Correspondence
Diabetic Nephropathy
N Engl J Med 2002; 347:947-948September 19, 2002
- Article
To the Editor:
In their Clinical Practice article, Remuzzi et al. (April 11 issue)1 recommend the use of an angiotensin-converting–enzyme (ACE) inhibitor or an angiotensin II–receptor antagonist as a reasonable first choice in a patient with type 2 diabetic nephropathy and a serum creatinine level of 1.5 mg per deciliter; they correctly recommend close follow-up of creatinine and potassium levels. We have observed that many doctors, even nephrologists, avoid the use of or stop using ACE inhibitors or angiotensin II-receptor antagonists in patients with a creatinine level higher than 2.5 to 3.0 mg per deciliter, perhaps because of concern about the risk of a progressive increase in creatinine and hyperkalemia. Although most clinical trials, such as the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan Study2 and the Irbesartan Diabetic Nephropathy Trial,3 have excluded patients with creatinine levels higher than 2.5 to 3.0 mg per deciliter, several post hoc analyses suggest that the absolute benefit of ACE inhibitors may be greater in patients with higher serum creatinine levels or a lower glomerular filtration rate.4,5 Patients with diabetic nephropathy should be referred to a nephrologist at an early stage of the disease. ACE inhibitors or angiotensin II–receptor antagonists remain an important antihypertensive strategy in patients with more advanced renal insufficiency.
5 ReferencesAtsuo Goto, M.D.
University of Tokyo Hospital, Tokyo 113-8655, Japan
agoto-tky@umin.ac. jp 1
Remuzzi G ,Schieppati A ,Ruggenenti P . Nephropathy in patients with type 2 diabetes. N Engl J Med 2002;346:1145-1151
Full Text | Web of Science | Medline2
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
Full Text | Web of Science | Medline3
Lewis EJ ,Hunsicker LG ,Clarke WR , et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345:851-860
Full Text | Web of Science | Medline4
Breyer JA ,Hunsicker LG ,Bain RP ,Lewis EJ . Angiotensin-converting-enzyme inhibition in diabetic nephropathy. Kidney Int Suppl 1994;45:S156-S160
Medline5
Ruggenenti P ,Perna A ,Remuzzi G . ACE inhibitors to prevent end-stage renal disease: when to start and why possibly never to stop: a post hoc analysis of the REIN trial results. J Am Soc Nephrol 2001;12:2832-2837
Web of Science | Medline
To the Editor:
In addition to the recommendations of Remuzzi et al., we would suggest two points. First, even after overt or incipient diabetic nephropathy has been diagnosed, physicians should remain alert to the possibility of secondary nondiabetic renal diseases whenever the clinical course rapidly worsens or has atypical features. Second, for the prevention of additional nephrotoxicity in patients with diabetic nephropathy, drugs that interfere with renal prostaglandin synthesis, such as nonsteroidal antiinflammatory drugs and common analgesics, should be avoided,1 and radiographic-contrast agents should be used with great caution, after prophylaxis with adequate hydration and acetylcysteine.2
2 ReferencesKarl August Brensing, M.D.
Peter Raab, M.D.
Ulrich Frotscher, M.D.
Nephrology and Dialysis Center Bonn, 53179 Bonn, Germany
brensing.bonn@t-online. de 1
Fored CM ,Ejerblad E ,Lindblad P , et al. Acetaminophen, aspirin, and chronic renal failure. N Engl J Med 2001;345:1801-1808
Full Text | Web of Science | Medline2
Tepel M ,van der Giet M ,Schwarzfeld C ,Laufer U ,Liermann D ,Zidek W . Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med 2000;343:180-184
Full Text | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: We agree with Dr. Goto that ACE inhibitors and angiotensin II–receptor antagonists also have an important renoprotective effect in patients with more severe renal insufficiency. In the collaborative study of captopril,1 most of the beneficial effect of treatment with captopril on the combined end point (a doubling of the base-line serum creatinine level, dialysis, or death) was observed in patients with basal serum creatinine values greater than 1.5 mg per deciliter. In this group, the higher the basal serum creatinine level, the greater the beneficial effect of ACE inhibition. Post hoc analyses of the data from the Ramipril Efficacy in Nephropathy study2 showed that in nondiabetic patients with proteinuric nephropathy, ramipril decreased the rate of decline in the glomerular filtration rate to a similar extent when the basal glomerular filtration rate was below or above 30 ml per minute per 1.73 m2 of body-surface area. In occasional patients, premature withdrawal of ramipril because of worsening serum creatinine values heralded an acceleration of the decline in the glomerular filtration rate and of progression to end-stage renal disease.
The point, made by Dr. Brensing and colleagues, that a secondary nondiabetic renal disease is possible even after overt or incipient nephropathy has been diagnosed, is well taken. One study showed that about two thirds of patients with type 2 diabetes and proteinuria had biopsy findings of nondiabetic renal disease associated with diabetic-type lesions.3 However, the progression of disease was mainly dependent on the degree of proteinuria rather than on the type of renal lesions.
We agree that nonsteroidal antiinflammatory drugs should be avoided in patients with diabetes. However, the use of aspirin (100 to 325 mg per day) is a safe and inexpensive way to reduce cardiovascular complications in persons with diabetes and is usually not associated with renal toxicity. We also agree that prophylactic oral administration of the antioxidant acetylcysteine, along with hydration, may prevent the reduction in renal function induced by nonionic, low-osmolality contrast agents in patients with chronic renal insufficiency and diabetes.
3 ReferencesGiuseppe Remuzzi, M.D.
Arrigo Schieppati, M.D.
Piero Ruggenenti, M.D.
Mario Negri Institute for Pharmacological Research, 24100 Bergamo, Italy
gremuzzi@marionegri.it 1
Lewis EJ ,Hunsicker LG ,Bain RP ,Rohde RD . The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993;329:1456-1462[Erratum, N Engl J Med 1993;330:152.]
Full Text | Web of Science | Medline2
Ruggenenti P ,Perna A ,Remuzzi G . ACE inhibitors to prevent end-stage renal disease: when to start and why possibly never to stop: a post hoc analysis of the REIN trial results. J Am Soc Nephrol 2001;12:2832-2837
Web of Science | Medline3
Gambara V ,Mecca G ,Remuzzi G ,Bertani T . Heterogeneous nature of renal lesions in type II diabetes. J Am Soc Nephrol 1993;3:1458-1466
Web of Science | Medline
