Very Low Protein Diet or Dialysis in Uremic Elderly?
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00388648|
Recruitment Status : Completed
First Posted : October 17, 2006
Last Update Posted : October 17, 2006
|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
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||No Changes Posted|
|Current Secondary Outcome Measures ICMJE
||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|
|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|
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.
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
|Intervention ICMJE||Drug: mixture of amino and keto acids|
|Study Arms ICMJE||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Original Enrollment ICMJE||Same as current|
|Study Completion Date ICMJE||July 2005|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|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|
|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|
|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