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Very Low Protein Diet or Dialysis in Uremic Elderly?

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ClinicalTrials.gov Identifier: NCT00388648
Recruitment Status : Completed
First Posted : October 17, 2006
Last Update Posted : October 17, 2006
Sponsor:
Information provided by:
Università degli Studi di Brescia

Tracking Information
First Submitted Date  ICMJE October 16, 2006
First Posted Date  ICMJE October 17, 2006
Last Update Posted Date October 17, 2006
Study Start Date  ICMJE January 2000
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: October 16, 2006)
  • The primary hypotheses to be tested are whether, at least in the elderly:
  • the supplemented Very Low Protein Diet (VLPD) does not increase the risk of morbidity and mortality,
  • a prolonged period of VLPD can postpone the need for dialysis in elderly patients, and dialysis can start at a RRF lower than usually suggested.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2006)
the VLPD does not induce malnutrition.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Very Low Protein Diet or Dialysis in Uremic Elderly?
Official Title  ICMJE Efficacy and Safety of a Very Low Protein Diet in Postponing Dialysis in Elderly: a Prospective Randomized Multicenter Controlled Study
Brief Summary

There are no solid data on the real advantage of an early start of dialysis, as suggested by the DOQI guidelines. Uremic patients frequently have a poor nutritional status. However, we cannot distinguish between the detrimental effect on nutrition of too low a residual renal function or too long a period of low protein-diet, per se. However, it appears that a very-low-protein diet (VLPD) supplemented with essential amino acids and keto-analogs of amino acids, and with an adequate quantity of calories, can prevent hypoalbuminemia at the start of dialysis and can slow the progression of chronic renal failure.

EDTA and USRDS data suggest that most patients starting dialysis nowadays are elderly, who also have the highest incidence of morbidity and mortality. Moreover, hospitalization rate becomes higher after the start of dialysis compared to the pre-dialysis period.

Can an aminoacid-supplemented VLPD, prolonged beyond the GFR limits suggested by DOQI, offer elderly patients better survival and better quality of life than dialysis? The answer can only come from a prospective, randomized trial, in elderly patients, starting at the GFR values suggested by the NKF-DOQI for starting dialysis, comparing outcomes with a vegetarian VLPD supplemented with a mixture of keto-analogs of amino acids and essential amino acids, and with dialysis.

Detailed Description

An adequate dose of dialysis is needed, in order to improve patient outcome, in both peritoneal dialysis (PD) and extracorporeal dialysis (HD). The debate, however, has renewed interest in when to start dialysis. The NKF-DOQI group suggested using the amount of solute clearance for regular dialysis as a value for starting dialysis treatment, i.e. creatinine clearance 9-14 ml/min.

Elderly patients on dialysis have a low survival rate.In fact, according to the lombard Registry(a italian region), patients 70-75 years old survive 2.9/3.6 years (male/female) after the start of dialysis, those 75-80 years old 2.7/2.7 years, and those 80-85 years old 2.4/1.4 years. This low survival is largely due to the combined effects of aging and comorbidities, on which an early start of dialysis has no or very limited positive effects.

Moreover, the hemodialytic treatment might have more negative effects in the elderly: intermittent hemodynamic stress, continuous fluctuation of electrolytes, metabolites, acid-base equilibrium, and the bioincompatibility of the membrane. In PD patients, the negative effects are also related to episodes of peritonitis and to daily loss of protein and a higher frequency of malnutrition.

An early start of dialysis should improve survival and well-being, and reduce morbidity. But a rapid decline of residual renal function (RRF) is observed after the start of dialysis. Maintenance of RRF as long as possible is very important, because the kidneys do some things a dialysis membrane cannot do: tubular and endocrine function, larger clearances of middle molecules, some of them potentially toxic such as parathyroid hormone, granulocyte inhibitory protein, and substances inducing anorexia.

In a prospective study on CAPD patients, for every increase of 1 ml/min of GFR, the relative risk (RR) of death decreased 50%. In the CanUsa study, using the time-dependent Cox multivariate analysis, a 5% reduction in RR of death was observed for each 5L/week of residual renal GFR at baseline (7). These results suggest that, at least in elderly patients, the fast decline of GFR observed after the start of dialysis could be another cause of the low survival rate.

In our center, 42 elderly patients started a very-low-protein diet (VLPD: 0.3 g of protein/kg body weight), supplemented with a mixture of keto acids and amino acids when their creatinine clearance reached values usually considered as a parameter for starting dialysis. The survival of this group of patients was compared with that of 71 patients directly put onto dialysis with the same creatinine clearance at which we started the VLPD. Subsequently, 24 patients in the diet group started dialysis when their mean GFR was 3.9 ml/min, i.e. lower than the 7 ml/min usually considered adequate in PD patients and much lower than 9-14 ml/min suggested by the NKF-DOQI group.

In this retrospective, non-randomized study, survival was better in the patients treated with diet than patients with dialysis. This seems to bear out that RRF does more than a dialytic membrane and must be preserved as long as possible.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Uremia
  • Elderly (Aged >70)
  • Dialysis
  • Low Protein Diet
  • Survival
Intervention  ICMJE Drug: mixture of amino and keto acids
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE
 (submitted: October 16, 2006)
160
Original Enrollment  ICMJE Same as current
Study Completion Date  ICMJE July 2005
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. males or females >= 70 years of age
  2. RRF 5-7 ml/min/1.73 m2
  3. left ventricular ejection fraction >40%
  4. signed informed written consent

Exclusion Criteria:

  1. diabetes
  2. severe cerebral disease
  3. proteinuria >3 g/24 h
  4. severe hepatic failure
  5. active malignancy
  6. COPD requiring supplementary oxygen
  7. AIDS, or HIV-positive
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 70 Years to 95 Years   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00388648
Other Study ID Numbers  ICMJE NBs2000
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Università degli Studi di Brescia
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Giovanni c Cancarini, Prof University of Brescia (Italy)
PRS Account Università degli Studi di Brescia
Verification Date October 2006

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP