The Modification of Diet in Renal Disease Study

Chronic Renal Disease Clinical Trial

— MDRD  

Official title:

The Modification of Diet in Renal Disease Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04364113
• Other study ID #: MDRD U01DK035073
• Secondary ID: U01DK035073
• Status: Completed
• Phase: Phase 3
• Start date: January 1, 1989
• Est. completion date: December 31, 2000

Study information

• Verified date: April 2020
• Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The Modification of Diet in Renal Disease Trial is a multicenter randomized clinical trial for men and women aged 18-70 years with chronic renal disease who are not on dialysis and who have not had a kidney transplant. Study participants are randomized in a 2 × 2 factorial design to diets containing different amounts of protein and phosphorus and to two levels of blood pressure control. The prescribed modifications differ depending on the level of a patient's kidney function. The primary outcome variable to compare diet or blood pressure groups is each patient's slope (or the change) in glomerular filtration rate (GFR) with time.

Description:

Selection of patients is conducted in two periods: a screening period for initial determination of eligibility and a 3-month baseline period. The baseline period is used to instruct patients about study procedures; to assess GFR and dietary protein intake; and to control blood pressure according to standard medical practice. GFR, dietary protein, and urinary protein must meet the eligibility criteria at the end of the baseline period before an individual can be randomized.

Two different strata or studies are used depending on the level of an individual's GFR at the end of the baseline period. Study A is for individuals with a GFR from 25 to 55 ml/min/1.73 m^2 and a usual dietary protein intake of at least 0.90 g/kg/day, where kg are standard body weight. Study B is for persons with a baseline GFR from 13 to 24 ml/min/1.73 m^2 and no specification of protein intake.

Individuals who are randomized in the trial are prescribed one of three diets and one of two target mean arterial blood pressure goals (MAP). MAP is a weighted average of the diastolic and systolic blood pressures (two-thirds diastolic plus one-third systolic). The goals depend on the person's age. The moderate goal of 107 mm Hg is equivalent to a blood pressure of 140/90 mm Hg, the usual limits of normal blood pressure. The low-MAP goal of 92 mm Hg is a more strict level of control than usually achieved, equivalent to, for example, 125/75 mm Hg.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 840
• Est. completion date: December 31, 2000
• Est. primary completion date: January 31, 1993
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Increased serum creatinine: Men: 1.4-7.0 mg/dl, Women: 1.2-7.0 mg/dl, or other objective evidence of kidney disease

• Mean arterial blood pressure <=125 mm Hg

• GFR 13-55 ml/min/1.73 m^2

• Urinary protein excretion <10 g/day

• Protein intake >0.90 g/kg/day if GFR 25-55 ml/min/1.73 m^2

Exclusion Criteria:

• Insulin-dependent diabetes or fasting serum glucose >200 mg/dl

• Patient on dialysis

• Kidney transplant recipient

• Lactating or pregnant woman or woman planning to become pregnant within the time frame of the study

• Doubtful compliance

• Body weight <80% or >160% of standard body weight

• Serum albumin <3.0 g/dl

• Selected renal disorders: Upper or lower urinary tract obstruction, Renal artery stenosis, Branched or staghorn calculi, Cystinuria

• Serious medical conditions: Malignancy (excluding skin cancer) within 1 year, Heart failure, New York Heart Association class 3 or 4, Lung disease, Liver disease, Gastrointestinal disease, Chronic systemic infections, including AIDS, Collagen vascular disease (other than rheumatoid arthritis), Frequent hospitalizations or disability

• Drugs: Immunosuppressive agents, Corticosteroids in excess of replacement dosage for 2 months per year or more, Gold or penicillamine within past month, Salicylates: more than 20 tablets per week, Other nonsteroidal antiinflammatory agents more than 3 times per week in past 2 months, Investigational drugs

• Allergy to iothalamate or iodine

• Inability or unwillingness to give consent

Related Conditions & MeSH terms

• Chronic Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency, Chronic

Intervention

Other:
• Usual Protein Diet
The usual protein diet contains 1.30 g/kg/day protein and 16-20 mg/kg/day of Phosphorus
• Low Protein Diet
The low protein diet contains 0.575 g/kg/day protein and 5-10 mg/kg/day of Phosphorus
• Very Low Protein Diet
The very low protein diet contains 0.28 g/kg/day or protein, mg/kg/day of Phosphorus and a keto acid mixture.

Drug:
• Medications needed to maintain usual blood pressure
The MAP goal for the usual blood pressure group is <=107 mm Hg for ages 18-60 and <=113 for ages 61+. Pharmacological and non-pharmacological therapies will be used to achieve the desired blood pressure values. The recommended anti-hypertensive regimen is a angiotensin-converting-enzyme inhibitor with or without a diuretic agent; a calcium-channel blocker or other medications can be added as needed.
• Medications needed to maintain low blood pressure
The MAP goal for the low blood pressure group is <=92 mm Hg for ages 18-60 and <=98 for ages 61+. Pharmacological and non-pharmacological therapies will be used to achieve the desired blood pressure values. The recommended anti-hypertensive regimen is a angiotensin-converting-enzyme inhibitor with or without a diuretic agent; a calcium-channel blocker or other medications can be added as needed.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	The Cleveland Clinic

References & Publications (4)

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. — View Citation

Levey AS, Greene T, Beck GJ, Caggiula AW, Kusek JW, Hunsicker LG, Klahr S. Dietary protein restriction and the progression of chronic renal disease: what have all of the results of the MDRD study shown? Modification of Diet in Renal Disease Study group. J — View Citation

Levey AS, Greene T, Sarnak MJ, Wang X, Beck GJ, Kusek JW, Collins AJ, Kopple JD. Effect of dietary protein restriction on the progression of kidney disease: long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study. Am J Kidney Dis. 20 — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in GFR slope	Slopes will be calculated on the basis of the final baseline GFR and all follow-up values without adjustment for body surface area	Up to 4 years
Secondary	Dialysis or kidney transplantation	Time to first dialysis or kidney transplantation	3 years
Secondary	Death from any cause	Time to death from any cause	3 years
Secondary	Time to kidney failure	The onset of kidney failure was ascertained from the US Renal Data System (USRDS) and included starting dialysis or undergoing kidney transplant	Up to 10 years
Secondary	Time to kidney failure or death	The onset of kidney failure was ascertained from the US Renal Data System (USRDS) and included starting dialysis or undergoing kidney transplant. Data for death were obtained from the National Death Index	Up to 10 years