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MDRD

23 juin 2016

MDRD? : Modification of Diet in Renal Disease.

BACKGROUND :
Restricting protein intake and controlling hypertension delay the progression of renal disease in animals. We tested these interventions in 840 patients with various chronic renal diseases.
METHODS :
In study 1, 585 patients with glomerular filtration rates of 25 to 55 ml per minute per 1.73 m2 of body-surface area were randomly assigned to a usual-protein diet or a low-protein diet (1.3 or 0.58 g of protein per kilogram of body weight per day) and to a usual- or a low-blood-pressure group (mean arterial pressure, 107 or 92 mm Hg). In study 2, 255 patients with glomerular filtration rates of 13 to 24 ml per minute per 1.73 m2 were randomly assigned to the low-protein diet (0.58 g per kilogram per day) or a very-low-protein diet (0.28 g per kilogram per day) with a keto acid-amino acid supplement, and a usual- or a low-blood-pressure group (same values as those in study 1). An 18-to-45-month follow-up was planned, with monthly evaluations of the patients.
RESULTS :
The mean follow-up was 2.2 years. In study 1, the projected mean decline in the glomerular filtration rate at three years did not differ significantly between the diet groups or between the blood-pressure groups. As compared with the usual-protein group and the usual-blood-pressure group, the low-protein group and the low-blood-pressure group had a more rapid decline in the glomerular filtration rate during the first four months after randomization and a slower decline thereafter. In study 2, the very-low-protein group had a marginally slower decline in the glomerular filtration rate than did the low-protein group (P = 0.07). There was no delay in the time to the occurrence of end-stage renal disease or death. In both studies, patients in the low-blood-pressure group who had more pronounced proteinuria at base line had a significantly slower rate of decline in the glomerular filtration rate.
CONCLUSIONS :
Among patients with moderate renal insufficiency, the slower decline in renal function that started four months after the introduction of a low-protein diet suggests a small benefit of this dietary intervention. Among patients with more severe renal insufficiency, a very-low-protein diet, as compared with a low-protein diet, did not significantly slow the progression of renal disease.

Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW, Striker G. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group. N Engl J Med. 1994 ;330:877-84. pdf

OBJECTIVE :
To examine the relations among proteinuria, prescribed and achieved blood pressure, and decline in glomerular filtration rate in the Modification of Diet in Renal Disease Study.

DESIGN :
2 randomized trials in patients with chronic renal diseases of diverse cause.

SETTING :
15 outpatient nephrology practices at university hospitals.

PATIENTS :
840 patients, of whom 585 were in study A (glomerular filtration rate, 25 to 55 mliters/min.1.73 m2) and 255 were in study B (glomerular filtration rate, 13 to 24 mliters/min.1.73 m2). Diabetic patients who required insulin were excluded.

INTERVENTIONS :
Patients were randomly assigned to a usual blood pressure goal (target mean arterial pressure, < or = 107 mm Hg for patients < or = 60 years of age and < or = 113 mm Hg for patients > or = 61 years of age) or a low blood pressure goal (target mean arterial pressure, < or = 92 mm Hg for patients < or = 60 years of age and < or = 98 mm Hg for patients > or = 61 years of age).
MAIN OUTCOME MEASURES :
Rate of decline in glomerular filtration rate and change in proteinuria during follow-up.

RESULTS :
The low blood pressure goal had a greater beneficial effect in persons with higher baseline proteinuria in both study A (P = 0.02) and study B (P = 0.01). Glomerular filtration rate declined faster in patients with higher achieved blood pressure during follow-up in both study A (r = -0.20 ; P < 0.001) and study B (r = -0.34 ; P < 0.001), and these correlations were stronger in persons with higher baseline proteinuria (P < 0.001 in study A ; P < 0.01 in study B). In study A, the association between decline in glomerular filtration rate and achieved follow-up blood pressure was nonlinear (P = 0.011) and was stronger at higher mean arterial pressure. In both studies, the low blood pressure goal significantly reduced proteinuria during the first 4 months after randomization. This, in turn, correlated with a slower subsequent decline in glomerular filtration rate.

CONCLUSIONS :
Our study supports the concept that proteinuria is an independent risk factor for the progression of renal disease. For patients with proteinuria of more than 1 g/d, we suggest a target blood pressure of less than 92 mm Hg (125/75 mm Hg). For patients with proteinuria of 0.25 to 1.0 g/d, a target mean arterial pressure of less than 98 mm Hg (about 130/80 mm Hg) may be advisable. The extent to which lowering blood pressure reduces proteinuria may be a measure of the effectiveness of this therapy in slowing the progression of renal disease.

Peterson JC, Adler S, Burkart JM, Greene T, Hebert LA, Hunsicker LG, King AJ, Klahr S, Massry SG, Seifter JL. Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study. Ann Intern Med. 1995 ;123:754-62. 7574193

Effects of dietary protein restriction on the progression of moderate renal disease in the Modification of Diet in Renal Disease Study.J Am Soc Nephrol. 1996 Dec ;7(12):2616-26. Erratum in : J Am Soc Nephrol 1997 Mar ; 8(3):493. 8989740

Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease Study.Levey AS, Adler S, Caggiula AW, England BK, Greene T, Hunsicker LG, Kusek JW, Rogers NL, Teschan PE.
Am J Kidney Dis. 1996 May ; 27(5):652-63. 8629624

Short-term effects of protein intake, blood pressure, and antihypertensive therapy on glomerular filtration rate in the Modification of Diet in Renal Disease Study. J Am Soc Nephrol. 1996 Oct ;7(10):2097-109. 8915969

Sarnak MJ, Greene T, Wang X, Beck G, Kusek JW, Collins AJ, Levey AS. The effect of a lower target blood pressure on the progression of kidney disease : long-term follow-up of the modification of diet in renal disease study. Ann Intern Med. 2005 Mar 1 ; 142(5):342-51. 15738453

The Modification of Diet in Renal Disease Study : design, methods, and results from the feasibility study. Am J Kidney Dis. 1992 Jul ;20(1):18-33. 1621675

Lazarus JM, Bourgoignie JJ, Buckalew VM, et al. Achievement and safety of a low blood pressure goal in chronic renal disease. The Modification of Diet in Renal Disease Study Group. Hypertension.1997 Feb ;29(2):641-50. 9040451

Hebert LA, Kusek JW, Greene T, et al. Effects of blood pressure control on progressive renal disease in blacks and whites. Modification of Diet in Renal Disease Study Group. Hypertension.1997 Sep ;30(3 Pt 1):428-35. 9314428

Buckalew VM Jr, Berg RL, Wang SR, Porush JG, Rauch S, Schulman G. Prevalence of hypertension in 1,795 subjects with chronic renal disease : the modification of diet in renal disease study baseline cohort. Modification of Diet in Renal Disease Study Group. Am J Kidney Dis.1996 Dec ;28(6):811-21. 8957032