Very Low Protein Diet or Dialysis in Uremic Elderly?
Condition: Uremia; Elderly (Aged >70); Dialysis; Low Protein Diet; Survival
MeSH terms: Uremia
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): mixture of amino and keto acids
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: Dialysis; Vegan Diet; Mortality; Morbidity; Treatment outcome