The n e w e ng l a n d j o u r na l of m e dic i n e

onary artery disease in the Coronary Artery Surgery Study invite indirect comparisons between PCI and CABG
(CASS). J Am Coll Cardiol 1993;22:1141-54.
5. Gavard JA, Chaitman BR, Sakai S, et al. Prognostic signifi- among physicians faced with the clinical decision
cance of elevated creatine kinase MB after coronary bypass sur- of which choice of revascularization is best suited
gery and after an acute coronary syndrome: results from the for a given patient, particularly if the goal of revas-
GUARDIAN trial. J Thorac Cardiovasc Surg 2003;126:807-13.
cularization is to reduce long-term clinical events
(especially myocardial infarction). Our recommen-
The Editorialists Reply: Garratt and Bailey dation that CABG surgery is the preferred approach
suggest that our statement that CABG surgery is to revascularization in patients with diabetes and
the preferred approach to revascularization in pa- stable coronary disease is further supported by
tients with diabetes and stable coronary disease two other randomized trials1,2 and a recent meta-
was not factual. We respectfully disagree. We clear- analysis.3
ly emphasized that among such patients who re-
mained symptomatic despite intensive treatment William E. Boden, M.D.
or who had substantial ischemia or extensive cor- State University of New York at Buffalo
onary artery disease, revascularization with either Buffalo, NY
PCI or CABG was reasonable and appropriate. We David P. Taggart, M.D., Ph.D.
explicitly acknowledged that the BARI 2D design Oxford University
precluded any direct comparison between PCI and Oxford, United Kingdom
CABG with regard to clinical outcomes. However, 1. BARI Investigators. The final 10-year follow-up results from
we reasoned that the option of either PCI or the BARI randomized trial. J Am Coll Cardiol 2007;49:1600-6.
CABG for revascularization, depending on the ana- 2. Serruys PW, Morice M-C, Kappetein AP, et al. Percutaneous
coronary intervention versus coronary-artery bypass grafting for
tomical complexity of coronary disease, is a real- severe coronary artery disease. N Engl J Med 2009;360:961-72.
world strength of the trial. In addition, the signifi- 3. Hlatky MA, Boothroyd DB, Bravata DM, et al. Coronary ar-
cant reduction in the composite end point (death, tery bypass surgery compared with percutaneous coronary inter-
ventions for multivessel disease: a collaborative analysis of indi-
myocardial infarction, or stroke) in patients with vidual patient data from ten randomised trials. Lancet 2009;
diabetes who underwent CABG would inevitably 373:1190-7.

Renal and Retinal Effects of Enalapril and Losartan

in Type 1 Diabetes
To the Editor: Mauer et al. (July 2 issue)1 used
structural hallmarks of diabetic renal disease to
show that early blockade of the renin–angiotensin
system did not slow progression of type 1 diabetic
nephropathy. The study excluded patients whose
blood pressure was greater than 135/85 mm Hg.
This may have had a major effect on study out-
come. First, not all patients with type 1 diabetes
are at risk for the development of nephropathy. In
contrast to retinopathy, diabetic nephropathy de-
velops in less than 50% of patients with type 1 dia-
betes.2,3 Arterial hypertension clearly contributes
to the predisposition for diabetic nephropathy.3
Mauer et al. demonstrated that marked mesangial
expansion develops in particular in patients with
hypertension. Therefore, the exclusion of patients
with hypertension may have resulted not only in
the selection of patients lacking a predisposition
for nephropathy but also in a selection of patients
less prone to progression of mesangial fractional
volume, the primary end point of the study. Se-
lection of a relatively healthy subgroup of patients
seems to be in line with the observed lower-than-
expected progression of mesangial expansion.
Jouke T. Tamsma, M.D., Ph.D.
Leiden University Medical Center
Leiden, the Netherlands
jttamsma@lumc.nl
1. Mauer M, Zinman B, Gardiner R, et al. Renal and retinal
effects of enalapril and losartan in type 1 diabetes. N Engl J Med
2009;361:40-51.
2. Seaquist ER, Goetz FC, Rick S, Barbosa J. Familial clustering
of diabetic kidney disease: evidence for genetic susceptibility to
diabetic nephropathy. N Engl J Med 1989;320:1161-5.
3. Krolewski AS, Canessa M, Warram JH, et al. Predisposition
to hypertension and susceptibility to renal disease in insulin-
dependent diabetes mellitus. N Engl J Med 1988;318:140-5.
To the Editor: The article by Mauer et al. dem-
onstrated that early blockade of the renin–angio-

1410 n engl j med 361;14  nejm.org  october 1, 2009

The New England Journal of Medicine

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Copyright © 2009 Massachusetts Medical Society. All rights reserved.
 correspondence

tensin system in patients with type 1 diabetes did
not slow nephropathy progression but slowed the
progression of retinopathy. These findings may
stimulate the widespread use of blockers of the
renin–angiotensin system in normotensive pa-
tients with type 1 diabetes and normoalbuminu-
ria. However, a higher incidence of microalbu-
minuria in the losartan group, which had the
best retinopathy outcome, raises concern about
possible adverse renal effects of blockade of the
renin–angiotensin system in these patients. Do
we have to trade nephropathy for retinopathy?
Further studies are warranted, but a closer look
into the data in the study by Mauer et al. might
help clarify this question. For instance, the renal
outcomes of patients without retinopathy pro-
gression in each group should be compared. Un-
til more data are available, we would think that
blockade of the renin–angiotensin system in
normotensive patients with type 1 diabetes and
normoalbuminuria, even with angiotensin-con-
verting–enzyme inhibitors, should not be gener-
ally recommended.
Pisut Katavetin, M.D.
Chulalongkorn University
Bangkok, Thailand
pkatavetin@yahoo.com
Paravee Katavetin, M.D.
Thonburi Hospital
Bangkok, Thailand
sion is an important precondition for early mes-
angial expansion. In fact, earlier studies strongly
suggested that hypertension in patients with type
1 diabetes is more likely the consequence than
the cause of mesangial expansion.1 Nevertheless,
the results of the Renin–Angiotensin System
Study (RASS) should not be extrapolated to the
relatively uncommon circumstance of patients
with diabetes, normoalbuminuria, normal or in-
creased glomerular filtration rate, and systemic
hypertension. The fact remains that the large
majority of patients with diabetes and normoal-
buminuria are normotensive, and renal benefits
from blockade of the renin–angiotensin system
could not be demonstrated in such patients. If
precise early predictors of diabetic nephropathy
become available, new studies including only pa-
tients at high risk would be warranted. In regard
to the suggestion by Katavetin and Katavetin
about patients without retinopathy progression,
the RASS does not have sufficient power for this
kind of subanalysis. We agree that further stud-
ies are warranted.
Michael Mauer, M.D.
University of Minnesota
Minneapolis, MN
mauer002@umn.edu
Bernard Zinman, M.D.
University of Toronto
Toronto, ON, Canada

Ronald Klein, M.D., M.P.H.

The authors reply: Although genetic predispo-
sition to hypertension is associated with an in-
creased risk of diabetic nephropathy in patients
with type 1 diabetes, as Tamsma correctly points
out, this does not mean that systemic hyperten-
University of Wisconsin
Madison, WI
1. Osterby R, Parving HH, Nyberg G, Hommel E, Mauer SM,
Steffes MW. Morphology of diabetic glomerulopathy and rela-
tionship to hypertension. Diabete Metab 1989;15:278-83.

Rhabdomyolysis and Acute Kidney Injury

To the Editor: Bosch and colleagues (July 2 is-
sue)1 observe that although conventional hemo-
dialysis filters do not remove myoglobin (molec-
ular weight, 17.8 kD), hemodiafiltration with
super-high-flux dialyzers may be effective.2 We
used a hemodialysis prescription with a super-high-
flux dialyzer (HCO-1100, Gambro) that efficient-
ly removed molecules of up to 60 kD. In two pa-
tients with rhabdomyolysis and acute kidney injury,
the mean serum myoglobin clearance with a sin-
gle dialysis treatment was 59%.3 A 4-hour dialy-
sis treatment cleared myoglobin from the equiva-
lent of 9 liters of extravascular fluid (twice the
intravascular volume). The kinetics of myoglobin
that we observed were similar to the kinetics of
free light chains (25 to 50 kD).4
The experience gained in the use of super-high-
flux dialysis to remove free light chains in myelo-

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Copyright © 2009 Massachusetts Medical Society. All rights reserved.