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The Preferred Diuretic in Diabetic Nephropathy
Which diuretic should be preferred in diabetic nephropathy with edema
and normal creatinine values or with compromised renal function and
creatinine levels around 2-3 mg/dL?
1. Furosemide
2. Chlorthiazide
3. Bumetanide
4. Hydrochlorthiazide
5. 1 & 3
Diabetic nephropathy, with its associated hypertension, is a fluid expansion/sodium
retention state, although the reasons may differ between type 1 and
type 2 diabetes. In type 1 diabetes, hypertension and fluid retention
are almost entirely due to glomerular and tubular damage, thus they
become manifest with increasing albuminuria.[1] In type 2 diabetes,
hypertension is present in over 25% of patients at diagnosis and is
a part of the metabolic syndrome of insulin resistance. The resulting
hyperinsulinemia has secondary effects on the renal tubule, leading
to salt and water retention and sympathetic nervous system activation.[2]
Other factors that may lead to edema are peripheral neuropathy, hypoalbuminemia
secondary to nephrosis, local vascular factors such as venous insufficiency,
and possible drug-induced effects -- for example, dihydropyridine calcium
channel blocking agents. Thus there are several potential causes, and
it is important to exclude them because, of course, not all will reflect
sodium/fluid overload and thus be responsive to diuretics.
Assuming that the edema is due to nephropathy and not nephrosis and
is associated with hypertension, then treatment is an important part
of blood pressure control and consequent nephroprotection. In these
circumstances, a loop diuretic such as furosemide or bumetanide is required,
because low-dose thiazides are often not potent enough and higher doses
can have unwanted metabolic effects on glycemia and lipidemia.[3] The
early studies of Parving and others[4] of blood pressure treatment in
type 1 diabetic nephropathy used furosemide as a key component of the
treatment regimen. In the RENAAL (Reduction of Endpoints in NIDDM with
the Angiotensin II Antagonist Losartan) study of losartan in type 2
diabetic nephropathy,[5] around 58% of patients were on a diuretic at
the outset and 84% at the end (mean follow-up, 3.4 years). These patients
had a mean baseline serum creatinine of 1.9 mg/dL. In the IDNT (Irbesartan
Diabetic Nephropathy Trial) of irbesartan vs amlodipine vs conventional
antihypertensive therapy in type 2 nephropathy,[6] investigators have
reported that split doses of loop diuretics were particularly effective
(unpublished but discussed at investigator meetings). The synergistic
effect of diuretics and drugs that block the renin-angiotensin system
makes them an integral part of most modern antihypertensive regimens
in diabetic nephropathy. It is worth mentioning, however, that dietary
salt restriction will also augment the hypotensive action of this combination.
References
1. Christlieb AR, Warram JH, Krolewski AS, et al. Hypertension: the
major risk factor in juvenile-onset insulin dependent diabetics. Diabetes.
1981;30(suppl 2):90-96.
2. Morris AD, Petrie JR Connell JMC. Insulin and hypertension. J Hypertens.
1994;12: 633-642. Abstract
3. Harper R, Atkinson AB, Bell PM. Should we use thiazide diuretics
in hypertensive patients with non-insulin-dependent diabetes mellitus?
QJM. 1996;89:477-482.
4. Parving H-H, Andersen AR, Smidt UM, et al. Effect of antihypertensive
treatment on kidney function in diabetic nephropathy. BMJ. 1987;294:1443-1147.
Abstract
5. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on
renal and cardiovascular outcomes in patients with type 2 diabetes and
nephropathy. N Engl J Med. 2001;345:861-869. Abstract
6. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of
the angiotensin-receptor antagonist irbesartan in patients with nephropathy
and type 2 diabetes. N Engl J Med. 2001;345:851-860. Abstract
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