- Click here for explanation of classification scheme.

The purpose of this secondary analysis of the MDRD Study was to determine the relationship between achieved in addition to prescribed, protein intake and the progression of kidney disease.

1. 18 to 70 years of age

2. Serum creatinine: 1.2 to 7.0 mg/dL (women) or 1.4 to 7.0 mg/dL (men) or CrCl <70 ml/min/1.73 m2.

3. Mean arterial blood pressure (MAP): <125 mm Hg

1. Systemic disease

2. Diabetes mellitus requiring insulin

3. Urine protein > 10 g/day

4. Body weight <80% or >160% of standard body weight

Recruitment Subjects were recruited from 15 clinical centers in the US.

Design:

Randomized Controlled Trial. Randomization was stratified according to clinical center and average MAP during baseline.

Blinding (if applicable):  Not mentioned

Intervention (if applicable):

a. protein: subjects were randomly assigned to follow either a low protein diet, 0.58 g/kg/d (>0.35 g/kg/d as HBV protein) or a very low protein diet (0.28 g/kg/d) + a mixture of amino and keto acids (0.28 g/kg/d) which provided a total of 0.46 g protein/kg/d. (1 additional g of protein was allowed for each g of urinary protein)

 b. phosphorus: low protein diet (5 to 10 mg/kd/day or very low protein diet (4 to 9 mg/kg/day)

Statistical Analysis

Baseline characteristics were compared between groups using t-test, ANOVA or chi-square tests, as appropriate. hypothesis tests were regarded as statistically significant if P less than or equal to 0.05 (two-sided). The decline in GFE was compared between the diet groups using a one-slope informative censoring model .

Timing of Measurements

Dietitians at each clinical center provided nutrition education to enable subjects to follow the diet protocol during the baseline period.

Estimated dietary protein intake was determined monthly using urea nitrogen excretion (UUN): protein intake (g/d) = 6.25 x [UUN (g/d) + standard body weight (kg) x 0.03] (g/kg standard body weight)/d ]

Intake of protein, phosphorus, calories, and other nutrients was assessed monthly from 3-day food records. Blood pressure and weight were measured monthly. Blood samples were analyzed for hematologic and biochemical values every 2 months.

GFR was measured at baseline, 2 months, 4 months, and every 4 months thereafter as the renal clearance of 125I-iothalamate. Symptoms of uremai were assessed monthly by a self-administered questionnaire.

Dependent Variables

• Rate of change of GFR (slope)
• Serum creatinine
• Creatinine clearance
• UUN
• Mean arterial pressure

Independent Variables

• low protein diet, 0.58 g/kg/d (>0.35 g/kg/d as HBV protein), phosphorus:5 to 10 mg/kd/day
• very low protein diet (0.28 g/kg/d) + a mixture of amino and keto acids (0.28 g/kg/d) which provided a total of 0.46 g protein/kg/d. (1 additional g of protein was allowed for each g of urinary protein), phosphorus 4 to 9 mg/kg/day.

Control Variables

Initial N: 255 patients 

Attrition (final N): 121 reached kidney failure and 7 died prior to an administrative censoring date of June 15, 1993 ~5 months after the final follow-up visit.   GFR measurements at 1, 2 and 3 years in 219, 137 and 62 patients.

Age:  Ranged from18 to 70 years.

Ethnicity: not stated

Other relevant demographics:  Not stated

Anthropometrics  Not stated

Location: 15 clinical centers in the U.S.

 

Baseline Renal Function was similar in the low protein (LP) and very low protein (VLP) diet groups:

	LP	VLP
GFR (ml/min/1.73 m2)	18.7+3.2	18.3+3.5
CrCl (ml/min/1.73 m2)	24.2+6.3	24.9+7.8
Serum creatinine (mg/dL)	3.5+0.9	3.4+0.9
Urine protein (g/d)	0.6+1.7*	0.5+1.8*
Estimated protein intake (g/kg/d)	0.9+0.2	0.9+0.2

* geometric mean

Other findings: 

 Inclusion of the amino acids in the supplement as a source of nitrogen in the very low protein diet group resulted in a mean total protein intake (food + supplements) of 0.66 g/kg/d which was slightly but significantly different from the low protein diet group (P<0.001) (a difference of 0.07 g/kg/d).

Rate of decline of GFR:

There was a significant inverse relationship between GFR and dietary protein intake (-2.94 and –4.32 mL/min/yr per g/kg/d without and with supplement respectively; P=0.026 and P=0.030).

In correlational analyses, we combined patients assigned to both diets and controlled for baseline factors associated with a faster progression of kidney disease. A 0.2 g/kg/d lower achieved total protein intake (food + supplement) was associated with a 1.15 mL/min/yr slower mean decline in GFR (P=0.011), equivalent to 29% of the mean GFR decline. After adjusting for achieved total protein intake, no independent effect of prescription of the keto acid-amino acid supplement to slow the GFR decline could be detected.

The mean follow-up protein intakes were 0.73 and 0.43 (food only) g/kg/day in the low and very low protein diet groups (P<0.001).

The secondary analysis of the MDRD Study suggest that a lower protein intake, but not the keto-amino acid supplement, retards the progression of advanced kidney disease. .

It is difficult to compare the value of delaying the onset of kidney failure to the difficulty in long-term adherence to a low-protein diet. We believe, however, that appropriate counseling by physicians and dietitians will enable patients to make this assessment. For well-informed patients who choose to restrict dietary protein, we recommend a prescribed protein intake of 0.6 g/kg/day in patients with a GFR <25 ml/min/1.732 . The benefit of this level of protein restriction in those with a GFR >25 ml/min remains to be determined..

 

Government:

NIDDK

This study demonstrates how difficult it is to reduce dietary protein intake to prescribed levels. Subjects instructed to follow a diet containing 0.58 g/kg/d achieved 0.73 g/kg/d compared to a baseline intake of 0.9 g/kg/d. In this study, the subjects saw a dietitian monthly throughout the study.