427
2006
20-40% ( ESRD )
30 299 mg ( )
( 300 mg/day )
dihydropyridine calcium channel blockers ( DCCBs )
non- DCCBs ( -blockers ( diuretics )
0 . 8 ( 10%)
60 ml/min per 1.73 m
230 ml/min per 1.73 m
2( Diabetic nephropathy)
( Microalbuminuria )
( Macroalbuminuria )
20-40% ( ES- RD )
30 299 ( )
1-2
( 300 mg/day )
3-4
5-6 7-8
1998 United Kingdom Prospective Diabetes Study ( UKPDS )
9
( a n g i o t e n s i n - c o n v e r t i n g e n z y m e
inhibitors ACEIs ) ( 140
mmHg )
( glomerular filtration rate GFR )
( )
13
( angiotension receptor blockers ARBs )
( ESRD )
14-16
17
dihy- dropyridine calcium channel blockers ( DCCBs )
18
non- DCCBs ( -blockers ) ( diuretics )
17,19
20-22
/
23
(1)
( ) (2) 24
( Angiotensin-converting enzyme inhibitors, ACEIs )
( Angiotension receptor blockers, ARBs
( Glomerular filtration rate, GFR )
)
24-25
( 24 )
( microalbuminuria )
30-299 g/mg ( ) ( macroalbuminuria )
300 g/mg
2 4
( urinary albumin excretion rate UAER )
( )
26
27-28
( 60 ml/min per 1.73 m
2)
26
Cockroft-Gault Levy
29( ( MDRD )
) http://www.kidney.
org/professionals/kdoqi/gfr_calculator.cfm.
60 ml/min per 1.73 m
230 ml/min per 1.73 m
230-31
2 4 GFR
(ml/min/1.73 m
2)
1
*≥ 90
2
*60-89
3 30-59
4 15-29
5 < 15
* 33
32
ADA
A-Level evidence B- Level evidence C-Level evidence Expert consensus
1.
/ ( A )
2.
/ ( A )
3.
0 . 8
( Recommended Dietary Allowances, RDA ) ( B )
1.
( E ) 2.
( E )
1.
( A ) 2.
(1)
( A ) (2)
( A ) (3)
( 1.5 mg/dl )
( A ) (4)
( E ) 3.
0.8 (
10% ) ( )
/
( B ) 4.
( B ) 5.
non- DCCBs ( -
blockers ) ( diuretics ) non- DCCBs
( E )
6.
( B )
7. /
( E )
8. 60 ml/min per
1.73 m
2( B )
1.Garg JP, Bakris GL. Microalbuminuria: marker of vascular dys- function, risk factor for cardiovascular disease. Vasc Med 2002;
7: 35-43.
2.Klausen K, Borch-Johnsen K, Feldt-Rasmussen B, et al. Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes. Circulation 2004; 110: 32- 5.
3.Gall MA, Hougaard P, Borch-Johnsen K, Parving HH. Risk fac- tors for development of incipient and overt diabetic nephropa- thy in patients with non-insulin dependent diabetes mellitus:
prospective, observational study. BMJ 1997; 314: 783-8.
4.Ravid M, Lang R, Rachmani R, Lishner M. Long-term reno- protective effect of angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus: a 7-year follow-up study. Arch Intern Med 1996; 156: 286-9.
5.Reichard P, Nilsson BY, Rosenqvist U. The effect of long-term intensified insulin treatment on the development of microvas- cular complications of diabetes mellitus. N Engl J Med 1993;
329: 304-9.
6.The Diabetes Control and Complications (DCCT) Research Group. Effect of intensive therapy on the development and pro- gression of diabetic nephropathy in the Diabetes Control and Complications Trial. Kidney Int 1995; 47: 1703-20.
7.UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-53.
8.UK Prospective Diabetes Study (UKPDS) Group. Effect of in- tensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854-65.
9.UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complica- tions in type 2 diabetes: UKPDS 38. BMJ 1998; 317: 703-13.
10.Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of an- giotensin-converting-enzyme inhibition on diabetic nephropa- thy: the Collaborative Study Group. N Engl J Med 1993; 329:
1456-62.
11.Laffel LM, McGill JB, Gans DJ. The beneficial effect of an-
giotensin-converting enzyme inhibition with captopril on dia- betic nephropathy in normotensive IDDM patients with mi- croalbuminuria: North American Microalbuminuria Study Group. Am J Med 1995; 99: 497-504.
12.Bakris GL, Williams M, Dworkin L, et al. Preserving renal func- tion in adults with hypertension and diabetes: a consensus ap- proach: National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis 2000;
36: 646-61.
13.Heart Outcomes Prevention Evaluation Study Investigators.
Effects of ramipril on cardiovascular and microvascular out- comes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet 2000; 355: 253-59.
14.Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective ef- fect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;
345: 851-60.
15.Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losar- tan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861-9.
16.Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P. The effect of irbesartan on the develop- ment of diabetic nephropathy in patients with type 2 diabetes.
N Engl J Med 2001; 345: 870-8.
17.Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al. A calci- um antagonist vs a non-calcium antagonist hypertension treat- ment strategy for patients with coronary artery disease: the International Verapamil-Trandolapril study (INVEST): a ran- domized controlled trial. JAMA 2003; 290: 2805-16.
18.Berl T, Hunsicker LG, Lewis JB, et al. Cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial of patients with type 2 diabetes and overt nephropathy. Ann Intern Med 2003;
138: 542-9.
19.Black HR, Elliott WJ, Grandits G, et al. Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. JAMA 2003; 289: 2073-82.
20.Pijls LT, de Vries H, Donker AJ, van Eijk JT. The effect of pro- tein restriction on albuminuria in patients with type 2 diabetes mellitus: a randomized trial. Nephrol Dial Transplant 1999; 14:
1445-53.
21.Pedrini MT, Levey AS, Lau J, Chalmers TC, Wang PH. The ef- fect of dietary protein restriction on the progression of diabetic and nondiabetic renal diseases: a meta-analysis. Ann Intern Med 1996; 124: 627-32.
22.Hansen HP, Tauber-Lassen E, Jensen BR, Parving HH. Effect of dietary protein restriction on prognosis in patients with diabe- tic nephropathy. Kidney Int 2002; 62: 220-8.
23.Kasiske BL, Lakatua JD, Ma JZ, Louis TA. A meta-analysis of the effects of dietary protein restriction on the rate of decline in renal function. Am J Kidney Dis 1998; 31: 954-61.
24.Eknoyan G, Hostetter T, Bakris GL, et al. Proteinuria and other
markers of chronic kidney disease: a position statement of the
National Kidney Foundation (NKF) and the National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK).
AmJKidney Dis 2003; 42: 617-22.
25.Meigs JB, Larson MG, D' Agostino RB, et al. Coronary artery calcification in type 2 diabetes and insulin resistance: the Framingham Offspring Study. Diabetes Care 2002; 25: 1313-9.
26.Kramer H, Molitch ME. Screening for kidney disease in adults with diabetes. Diabetes Care 2005; 28: 1813-6.
27.Kramer HJ, Nguyen QD, Curhan G, Hsu CY. Renal insufficien- cy in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus. JAMA 2003; 289: 3273-7.
28.Tsalamandris C, Allen TJ, Gilbert RE, et al. Progressive decline in renal function in diabetic patients with and without albumi- nuria. Diabetes 1994; 43: 649-55.
29.Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation: Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999; 130:
461-70.
30.Levinsky NG. Specialist evaluation in chronic kidney disease:
too little, too late. Ann Intern Med 2002; 137: 542-3.
31.American Diabetes Association. Nephropathy in diabetes (Position Statement). Diabetes Care 2004; 27 (Suppl.1): S79- 83.
32.American Diabetes Association. Standards of medical care in diabetes 2006 (Position Statement). Diabetes Care 2006; 29 (Suppl.1): S4-42.
33.National Kidney Foundation. K/DOQI clinical practice guide-
lines for chronic kidney disease: evaluation, classification, and
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2006 ADA Standard Recommendations for Treatment of Diabetic Nephropathy
Lyh-Jyh Hao, Chwen-Yi Yang
1, Ming-Jei Wu
2, Kuo-Liang Chai
3, Jin-Shiung Cheng
4, and Tain-Cheng Wu
4Diabetic nephropathy occurs in 20 40% of patients with diabetes and is the single leading cause of end- stage renal disease (ESRD). Persistent albuminuria in the range of 30 299 mg/day (microalbuminuria) has been shown to be the earliest stage of diabetic nephropathy in type 1 diabetes and a marker for development of nephropathy in type 2 diabetes. Microalbuminuria is also a well-established marker of increased cardiovascular disease (CVD) risk. Intensive diabetes management with the goal of achieving near normoglycemia has been shown in large prospective randomized studies to delay the onset of microalbuminuria and the progression of mi- cro- to macroalbuminuria( 300 mg/day) in patients with type 1 and type 2 diabetes. In the treatment of both mi- cro- and macroalbuminuria, either ACE inhibitors or ARBs should be used except during pregnancy. With regards to slowing the progression of nephropathy, the use of DCCBs as initial therapy is not more effective than place- bo. Their use in nephropathy should be restricted to additional therapy to further lower blood pressure in patients already treated with ACE inhibitors or ARBs. In patients unable to tolerate ACE inhibitors and/or ARBs, consid- er the use of non-DCCBs, -blockers, or diuretics for the management of blood pressure. Protein restriction is of benefit in slowing the progression of albuminuria, GFR decline, and occurrence of ESRD. With presence of nephropathy, initiate protein restriction to 0.8 g kg body wt
-1day
-1( 10% of daily calories). Serum creati- nine should be measured at least annually for the estimation of GFR in all adults with diabetes regardless of the degree of urine albumin excretion. Serum creatinine alone should not be used as a measure of kidney function, but used to estimate GFR and stage the level of CKD. Consider referral to a physician experienced in the care of diabetic renal disease either when the GFR has fallen to <60 ml/min per 1.73 m
2or if difficulties occur in the management of hypertension or hyperkalemia. It is suggested that consultation with a nephrologist be obtained when the GFR is <30 ml/min per 1.73 m
2. Early referral of such patients has been found to reduce cost and im- prove quality of care and keep people off dialysis longer. ( J Intern Med Taiwan 2006; 17: 99-105 )
Division of Endocrinology and Metabolism, Yung Kang Veterans Hospital.
1
Division of Endocrinology and Metabolism, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan.
2
Division of Nephrology, Yung Kang Veterans Hospital.
3
Department of Internal Medicine, Yung Kang Veterans Hospital.
4
