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[IP] Nephropathy was A Medscape article that might interest you:

Sorry, when I had the article forwarded to IP I thought they would send the
article, not just the link. I copied it and pasted here.

Denise Guerin
Is controlling blood pressure more important than controlling glycemia in
diabetic nephropathy?

from Rudy W. Bilous, MD, FRCP , 01/01/2003

This question often arises in mixed meetings of diabetologists and
nephrologists. It needs answers on several levels, depending on the stage of
nephropathy in question.

Treatments can be thought of in terms of primary prevention of nephropathy;
secondary prevention, ie, halting the progression from microalbuminuria to
clinical nephropathy; and tertiary prevention, ie, preventing progression from
clinical nephropathy to end-stage renal failure. It is also important to
realize that most studies in nephropathy have used the intermediate end point
of reduction in albuminuria. A few have looked at halting the decline of
glomerular filtration rate (GFR), either by direct measurement or by using the
proxy of a doubling of baseline serum creatinine. Very few have looked at the
development of end-stage renal failure, and, finally, very few have looked at
the outcome of reversal or prevention of renal pathologic changes.

So how do glycemic control and blood pressure lowering compare?

For primary prevention, glycemic control has all the evidence. Both the
Diabetes Control and Complications Trial (DCCT) in type 1[1] and the United
Kingdom Prospective Diabetes Study (UKPDS)[2] in type 2 diabetes showed that
intensive vs conventional therapy reduced the number of patients developing de
novo microalbuminuria. After 9 years, the HbA1c values were 9.1% vs 7.2% in
the DCCT and 8.4% vs 7.8% in the UKPDS. The cumulative incidence of
microalbuminuria (defined as an albumin excretion rate [AER] > 28 micrograms
(mcg)/min in the DCCT and an albumin concentration of > 50 mg/L in the UKPDS)
was 34.5% vs 21.4% and 25.4% vs 19.2% in the DCCT and UKPDS, respectively.
These data gave relative risks for intensive vs conventional of 0.61 (95%
confidence interval [CI] 0.48-0.79) and 0.76 (99% CI 0.62-0.91),

By contrast, there are no significant data showing that antihypertensive
therapies can prevent microalbuminuria development. Both the EUCLID (EURODIAB
Controlled Trial of Lisinopril in Insulin Dependent Diabetes)[3] and
MICROHOPE[4] studies showed a nonsignificant reduction in AER and
albumin/creatinine ratios, respectively.

In terms of secondary prevention of an increase in albuminuria to the
clinically proteinuric range (conventionally an albumin concentration > 300
mg/L or an AER > 200 mcg/min), the data favor antihypertensive therapy --
specifically renin-angiotensin blockade using angiotensin converting-enzyme
(ACE) inhibitors in type 1 and angiotensin II receptor blockers (ARB) in type

A meta-analysis of raw data from over 690 type 1 patients with
microalbuminuria and "normal" blood pressures treated with either an ACE
inhibitor or placebo showed a 75% reduction in AER at 1 year.[5] The odds
ratio (OR) for developing nephropathy was 0.38 for the ACE inhibitor-treated
group, who also had a 3.07 OR for regression to normoalbuminuria. The IRMA 2
study in 590 type 2 patients with hypertension and microalbuminuria had a
hazard ratio of 0.32 for nephropathy and around 1.6 for normoalbuminuria for
those treated with 300 mg/d irbesartan.[6]

Although early short-term studies from Scandinavia suggested that improved
glycemic control prevented an increase in albuminuria in microalbuminuric
patients, these results were not confirmed by the DCCT[7] or others.[8] The
UKPDS analyzed their data by achieved glycemia[9] and blood pressure.[10] They
found that whereas there was a 37% reduction in microvascular end points
(predominantly retinopathy) for each 1% lowering of HbA1c, the impact of a
10-mmHg lowering of blood pressure was associated with only a 13% reduction.

For tertiary prevention, there are no data suggesting that long-term intensive
glycemic control confers benefit. The Collaborative Study Group Trial of
captopril in type 1[11] and irbesartan[12] and losartan[13] in type 2
nephropathy conclusively showed a reduction in those developing end-stage
renal failure, and these benefits appeared to be renin-angiotensin system

What about GFR? Intensive glycemic control can reduce hyperfiltration in early
type 1 diabetes,[14] and glucose-lowering therapy also lowers GFR in newly
diagnosed type 2 patients.[15] The effect of this on long-term risk for
nephropathy development is uncertain. At the stage of microalbuminuria,
glycemic control had little effect on GFR in the DCCT.[7] Antihypertensive
therapy with ACE inhibitors actually reduces GFR in the short term in
microalbuminuric patients,[16] but seems to be associated with a stabilization
thereafter. In the UKPDS, the number of patients doubling baseline serum
creatinine over 12 years was significantly lower in the intensively managed
group. However, the actual numbers affected were only 7 vs 10 (0.91% vs
3.52%).[2] The previously mentioned captopril, irbesartan, and losartan trials
all showed significantly lower percentages of patients with nephropathy
doubling baseline serum creatinine (adjusted risk reductions 49%, 29%, and
25%, respectively).

Finally, the very few biopsy-based studies of renal structure have shown that
pancreas transplantation can prevent glomerulopathy developing in renal
allografts in type 1 diabetic patients,[17] and also a reversal of lesions in
native kidneys after 10 (but not 5) years.[18] Thus, the lesions may take as
long to reverse as they do to develop. The effect of antihypertensive
therapies on structure has only been studied for a maximum of 3 years, and no
significant impact was detected after this time.[19]

What conclusions can be drawn? First, glycemic control is the only therapy
shown to prevent nephropathy development and is the only treatment proven to
reverse established pathology. By the time AER is in the microalbuminuric or
nephropathic range, only antihypertensive therapy, specifically with ACE
inhibitors or ARB, can slow the pace of progression. However, it must be
remembered that good glycemic control continues to benefit nephropathy
throughout the diabetic patient's life and should be strived for at all times.
Both therapies remain the foundation stones of good care. The challenge is to
optimize them for all our patients.
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