The nutritional status of chronic renal failure patients following the initiation of hemodialysis treatment

Abstract

Related articles, pp. 133 and 143In this issue of the Journal, there are two papers1Mehrotra R Berman N Alistwani A Kopple JD Improvement of nutritional status after initiation of maintenance hemodialysis.Am J Kidney Dis. 2002; 40: 133-142Abstract Full Text Full Text PDF Scopus (72) Google Scholar, 2Pupim LB Kent P Caglar K Shyr Y Hakim RM Ikizler TA Improvement in nutritional parameters after initiation of chronic hemodialysis.Am J Kidney Dis. 2002; 40: 143-151Abstract Full Text Full Text PDF Scopus (61) Google Scholar with virtually identical titles and with the same conclusion; namely, that the initiation of chronic hemodialysis therapy in incident chronic renal failure patients is associated with improvement in nutritional status. These observations are clearly important in a number of areas such as the predialysis management of chronic renal insufficiency, when to initiate hemodialysis, subsequent nutritional status of patients on hemodialysis, and the influence of all of these on the long-term outcome of patients with chronic renal insufficiency. The MDRD Study confirmed the age-old wisdom that patients with progressive chronic renal failure will spontaneously limit their dietary protein intake in order to minimize the frequent gastrointestinal symptoms of advancing uremia.3Modification of Diet in Renal Disease Study Group prepared by J Kopple et al.Relationship between nutritional status and the glomerular filtration rate: Results from the MDRD study.Kidney Int. 2000; 57: 1688-1703Google Scholar With this are associated worsening parameters of nutritional status. Such patients have a high incidence of hypoalbuminemia and other evidence of protein and energy malnutrition by the time dialysis is instituted. Evidence of such malnutrition at the time of dialysis initiation has been found to influence subsequent survival and morbidity after dialysis has been initiated.4Kopple JD National Kidney Foundation K/DOQI Clinical Practice Guidelines for Nutrition in Renal Failure.Am J Kidney Dis. 2001; 37: S66-S70Google Scholar, 5Lowrie EG Huang WH Lew NL Death risk predictors among peritoneal dialysis and hemodialysis patients: A preliminary comparison.Am J Kidney Dis. 1995; 26: 220-228Google Scholar, 6Ikizler TA Evanson JA Greene JH Hakim RM Impact of nutritional status and residual renal function at initiation of hemodialysis on subsequent morbidity in chronic dialysis patients.J Am Soc Nephrol. 1996; 7: 1319Google Scholar Because of this, some were concerned about the use of low protein diets in attempts to slow down progression of chronic renal disease and began to recommend starting maintenance dialysis earlier in order to prevent such malnutrition.7National Kidney Foundation/Kidney-Dialysis Outcome Quality Initiative Clinical Practice Guidelines for nutrition in chronic renal failure.Am J Kidney Dis. 2000; 35: S1-S140Google Scholar On the other hand, others have pointed out the documented catabolic process induced by the hemodialysis procedure itself and the high mortality rate in dialysis patients as a justification for delaying the initiation of dialysis until uraemic symptomatology has developed.8Mitch WE Maroni BJ Nutritional considerations and the indications for dialysis.Am J Kidney Dis. 1998; 31: 185-194Abstract Full Text Full Text PDF Scopus (23) Google Scholar Until recently, little was known about the effect of dialysis initiation on serum albumin and other markers of nutritional status and on factors that might influence any such changes that occurred. These two reports provide excellent new information in this field.The first report is that of Drs Mehrotra, Berman, Allistwani, and Kopple from the Harbor-UCLA Medical Center.1Mehrotra R Berman N Alistwani A Kopple JD Improvement of nutritional status after initiation of maintenance hemodialysis.Am J Kidney Dis. 2002; 40: 133-142Abstract Full Text Full Text PDF Scopus (72) Google Scholar They studied 97 patients who were admitted to their outpatient dialysis unit within 30 days of initiation of maintenance hemodialysis and examined their routine laboratory tests from the time of that admission up until they had completed 6 months of regular hemodialysis therapy. Their results showed that between months 1 and 6 there were statistically significant increases in predialysis serum albumin, iron, transferrin saturation, creatinine, and the normalized protein equivalent of total nitrogen appearance (nPNA). Body weight declined initially until month 4 and then started to increase. There was a strong curvilinear relationship between the mean nPNA and the final serum albumin concentration achieved. They thus conclude that following the initiation of hemodialysis, there is an overall improvement in nutritional status that includes an increase in dietary protein intake (as measured by nPNA) and that the improvement in nutritional status may be related to this increase in dietary protein intake likely afforded by the relief of uraemic symptomatology by hemodialysis.The second study by Drs Pupim, Kent, Caglar, Shyr, Hakim, and Ikizler from Vanderbilt University Medical Center studied 50 incident hemodialysis patients at baseline and then every 3 months following the initiation of hemodialysis up to 1 year.2Pupim LB Kent P Caglar K Shyr Y Hakim RM Ikizler TA Improvement in nutritional parameters after initiation of chronic hemodialysis.Am J Kidney Dis. 2002; 40: 143-151Abstract Full Text Full Text PDF Scopus (61) Google Scholar They followed multiple nutritional markers including biochemical parameters as well as analysis of body composition by bioimpedance (BIA) and dual energy x-ray absorptiometry (DEXA); the latter being done only at baseline and at 12 months. Their results showed that at baseline the nutritional markers were well correlated among each other. Following the initiation of hemodialysis, there were marked improvements in most of the nutritional parameters, including serum albumin, serum prealbumin, nPNA, BIA, and DEXA-derived fat mass and BIA-derived reactance and phase angle, suggesting improvements in cellular health. The improvement in nutritional parameters was influenced by baseline nutritional status to the extent that even at the 12-month follow-up, the baseline nutritional parameters predicted the final study values. Their conclusions were also that initiation of maintenance hemodialysis therapy is associated with improvement in most of the nutritional markers. They point out that the nutritional benefits of the increased solute clearance provided by hemodialysis overruled its potential catabolic effects. An important finding was that the extent of improvement was dependent on the nutritional status at the time of initiation of dialysis.The two studies are very similar. They are virtually identical in study concept. The study patients had somewhat different demographic characteristics from the two areas: there being fewer African-American and more diabetic patients in the UCLA study. The Vanderbilt study examined more variables including body composition and also measured C-reactive protein (CRP) as an indicator of inflammation. The UCLA study1Mehrotra R Berman N Alistwani A Kopple JD Improvement of nutritional status after initiation of maintenance hemodialysis.Am J Kidney Dis. 2002; 40: 133-142Abstract Full Text Full Text PDF Scopus (72) Google Scholar invoked some very sophisticated statistical methodologies looking at slopes of change (eg, albumin) and the interrelations between various parameters such as albumin and nPNA. Nevertheless, the results can clearly be put together and create one story, namely that following the initiation of dialysis, the serum albumin will start to rise. To what extent it rises will depend on the age of the patient (the elderly being disadvantaged) and on the improvement of dietary protein intake as measured by nPNA. The nPNA is not influenced by catabolism as the CRP levels found by the Vanderbilt study2Pupim LB Kent P Caglar K Shyr Y Hakim RM Ikizler TA Improvement in nutritional parameters after initiation of chronic hemodialysis.Am J Kidney Dis. 2002; 40: 143-151Abstract Full Text Full Text PDF Scopus (61) Google Scholar were no different from beginning to end, and all analyses for trends in nutritional markers were reported following adjustments for CRP. The nPNA improvement plus other nutritional parameters were also independent of both residual renal function and any decrease in urinary protein losses from baseline over study time. Both studies showed an initial loss in body weight. The UCLA study1Mehrotra R Berman N Alistwani A Kopple JD Improvement of nutritional status after initiation of maintenance hemodialysis.Am J Kidney Dis. 2002; 40: 133-142Abstract Full Text Full Text PDF Scopus (72) Google Scholar surmised that this could be dependent on change in extracellular fluid volume from the initiation of dialysis. The Vanderbilt study2Pupim LB Kent P Caglar K Shyr Y Hakim RM Ikizler TA Improvement in nutritional parameters after initiation of chronic hemodialysis.Am J Kidney Dis. 2002; 40: 143-151Abstract Full Text Full Text PDF Scopus (61) Google Scholar confirms this by BIA. The UCLA study1Mehrotra R Berman N Alistwani A Kopple JD Improvement of nutritional status after initiation of maintenance hemodialysis.Am J Kidney Dis. 2002; 40: 133-142Abstract Full Text Full Text PDF Scopus (72) Google Scholar shows the trend to increase weight following the fourth month, which was felt due to an increase in lean body mass and, hence, might account for the increase in serum creatinine. The Vanderbilt study2Pupim LB Kent P Caglar K Shyr Y Hakim RM Ikizler TA Improvement in nutritional parameters after initiation of chronic hemodialysis.Am J Kidney Dis. 2002; 40: 143-151Abstract Full Text Full Text PDF Scopus (61) Google Scholar showed any increase in body weight to come after the ninth month, and this was not associated with DEXA evidence of increase in lean body mass but rather of fat content. The Vanderbilt team2Pupim LB Kent P Caglar K Shyr Y Hakim RM Ikizler TA Improvement in nutritional parameters after initiation of chronic hemodialysis.Am J Kidney Dis. 2002; 40: 143-151Abstract Full Text Full Text PDF Scopus (61) Google Scholar surmised that the increase in creatinine might be at least in part a reflection of the loss of renal function over time and that more studies were indicated in this area. The most important contribution of the UCLA paper1Mehrotra R Berman N Alistwani A Kopple JD Improvement of nutritional status after initiation of maintenance hemodialysis.Am J Kidney Dis. 2002; 40: 133-142Abstract Full Text Full Text PDF Scopus (72) Google Scholar is to point out the strong relationship between the mean nPNA (ie, dietary intake) following commencement of dialysis and the final serum albumin. The major contribution from the Vanderbilt study2Pupim LB Kent P Caglar K Shyr Y Hakim RM Ikizler TA Improvement in nutritional parameters after initiation of chronic hemodialysis.Am J Kidney Dis. 2002; 40: 143-151Abstract Full Text Full Text PDF Scopus (61) Google Scholar is to show that limitations on improvement relate to how poorly nourished the patient was at baseline.These two studies certainly point out that protein energy malnutrition is common in the predialysis patient and strongly suggest that the malnutrition has the potential for reversal following the commencement of dialysis therapy. The improvement that does take place is most likely due to the reversal of uremic toxicity and improvement in dietary protein and energy intake afforded by appetite improvement. The message given by the studies is that hemodialysis should be instituted before significant malnutrition takes place, especially so in the elderly, who are more likely to have poorer nutritional parameters at the initiation of dialysis and who respond less favorably to the dialysis therapy. Both of these studies are limited by the fact that they are observational in nature and are not randomized controlled studies. However, how can one do a randomized controlled study on the effect of dialysis initiation on nutritional status? Such a study would be likely unethical and certainly fraught with problems of defining the characteristics of a group to start dialysis where it is still safe to leave a control malnourished group for (say) a further 6-month period without dialysis. Do these studies, therefore, support the concept of the “early start” for dialysis therapy? They likely do, but how early and for who—all or only the malnourished? The Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD),9Korevaar JC Jansen MAM Dekker FW for the Netherlands Cooperative Study on the Adequacy of Dialysis Study Group et al.When to initiate dialysis: Effect of proposed US guidelines on survival.Lancet. 2001; 358: 1046-1050Abstract Full Text Full Text PDF Scopus (187) Google Scholar a large multicenter prospective cohort (not randomized) study showed that “timely” starters on dialysis by NKF-K/DOQI standards (ie, weekly Kt/V urea at start is greater than 2.0 or if less than 2.0, then nPNA is above 0.8 g/kg/d and body mass index is at least 20 kg/m2) had a small gain in survival time in the first 3 years after the start of dialysis over “late” starters. This gain, however, was felt to be purely a reflection of initiating dialysis earlier in the disease and the study did not identify the nPNA at dialysis initiation as influencing survival odds.9Korevaar JC Jansen MAM Dekker FW for the Netherlands Cooperative Study on the Adequacy of Dialysis Study Group et al.When to initiate dialysis: Effect of proposed US guidelines on survival.Lancet. 2001; 358: 1046-1050Abstract Full Text Full Text PDF Scopus (187) Google Scholar Perhaps only a randomized study with both malnourished and well-nourished patients at dialysis initiation will help. A North American randomized controlled study was considered to examine the influence of “early start” on longer term survival but following a pilot study was deemed to be impossible on logistical grounds (Churchill and Clase, personal communication). Such a study has, however, been started in Australia and New Zealand. This trial has the acronym IDEAL (Initiating Dialysis Early and Late) and, while powered for mortality, has several secondary endpoints and includes nutritional and morbidity substudies (C. Pollock, personal communication). We await those results with interest. These studies also bring back the concept that the dialysis treatment itself may have significant influence on nutritional parameters and, hence, on outcome. While this may be turning the clock back a whole decade and reopen the “nPNA/Kt/V controversy” intuitively, one has to believe that the adequacy of dialysis delivered and how it is delivered (high flux, low flux, peritoneal dialysis, hemodialysis, etc) has some influence upon dietary protein intake at least in protein malnourished uremic patients without the “malnutrition, inflammation, atherosclerosis” syndrome.10Efendic E Lindholm B Bergstrom J Stenvinkel P Strong association between malnutrition, inflammation and atherosclerosis in chronic renal failure.Kidney Int. 1999; 55: 1899-1911Google Scholar We now know the preliminary results of the HEMO study as far as survival is concerned. The secondary analyses of that study regarding dose and flux on nutritional parameters are also eagerly awaited.Until further information regarding nutrition, early start, dose, and flux is obtained, these current studies certainly give credence to the NKF-K/DOQI recommendations on the initiation of dialysis therapy on malnourished patients with advanced chronic renal failure in whom other interventions have failed to result in nutritional improvement.7National Kidney Foundation/Kidney-Dialysis Outcome Quality Initiative Clinical Practice Guidelines for nutrition in chronic renal failure.Am J Kidney Dis. 2000; 35: S1-S140Google Scholar Related articles, pp. 133 and 143 In this issue of the Journal, there are two papers1Mehrotra R Berman N Alistwani A Kopple JD Improvement of nutritional status after initiation of maintenance hemodialysis.Am J Kidney Dis. 2002; 40: 133-142Abstract Full Text Full Text PDF Scopus (72) Google Scholar, 2Pupim LB Kent P Caglar K Shyr Y Hakim RM Ikizler TA Improvement in nutritional parameters after initiation of chronic hemodialysis.Am J Kidney Dis. 2002; 40: 143-151Abstract Full Text Full Text PDF Scopus (61) Google Scholar with virtually identical titles and with the same conclusion; namely, that the initiation of chronic hemodialysis therapy in incident chronic renal failure patients is associated with improvement in nutritional status. These observations are clearly important in a number of areas such as the predialysis management of chronic renal insufficiency, when to initiate hemodialysis, subsequent nutritional status of patients on hemodialysis, and the influence of all of these on the long-term outcome of patients with chronic renal insufficiency. The MDRD Study confirmed the age-old wisdom that patients with progressive chronic renal failure will spontaneously limit their dietary protein intake in order to minimize the frequent gastrointestinal symptoms of advancing uremia.3Modification of Diet in Renal Disease Study Group prepared by J Kopple et al.Relationship between nutritional status and the glomerular filtration rate: Results from the MDRD study.Kidney Int. 2000; 57: 1688-1703Google Scholar With this are associated worsening parameters of nutritional status. Such patients have a high incidence of hypoalbuminemia and other evidence of protein and energy malnutrition by the time dialysis is instituted. Evidence of such malnutrition at the time of dialysis initiation has been found to influence subsequent survival and morbidity after dialysis has been initiated.4Kopple JD National Kidney Foundation K/DOQI Clinical Practice Guidelines for Nutrition in Renal Failure.Am J Kidney Dis. 2001; 37: S66-S70Google Scholar, 5Lowrie EG Huang WH Lew NL Death risk predictors among peritoneal dialysis and hemodialysis patients: A preliminary comparison.Am J Kidney Dis. 1995; 26: 220-228Google Scholar, 6Ikizler TA Evanson JA Greene JH Hakim RM Impact of nutritional status and residual renal function at initiation of hemodialysis on subsequent morbidity in chronic dialysis patients.J Am Soc Nephrol. 1996; 7: 1319Google Scholar Because of this, some were concerned about the use of low protein diets in attempts to slow down progression of chronic renal disease and began to recommend starting maintenance dialysis earlier in order to prevent such malnutrition.7National Kidney Foundation/Kidney-Dialysis Outcome Quality Initiative Clinical Practice Guidelines for nutrition in chronic renal failure.Am J Kidney Dis. 2000; 35: S1-S140Google Scholar On the other hand, others have pointed out the documented catabolic process induced by the hemodialysis procedure itself and the high mortality rate in dialysis patients as a justification for delaying the initiation of dialysis until uraemic symptomatology has developed.8Mitch WE Maroni BJ Nutritional considerations and the indications for dialysis.Am J Kidney Dis. 1998; 31: 185-194Abstract Full Text Full Text PDF Scopus (23) Google Scholar Until recently, little was known about the effect of dialysis initiation on serum albumin and other markers of nutritional status and on factors that might influence any such changes that occurred. These two reports provide excellent new information in this field. The first report is that of Drs Mehrotra, Berman, Allistwani, and Kopple from the Harbor-UCLA Medical Center.1Mehrotra R Berman N Alistwani A Kopple JD Improvement of nutritional status after initiation of maintenance hemodialysis.Am J Kidney Dis. 2002; 40: 133-142Abstract Full Text Full Text PDF Scopus (72) Google Scholar They studied 97 patients who were admitted to their outpatient dialysis unit within 30 days of initiation of maintenance hemodialysis and examined their routine laboratory tests from the time of that admission up until they had completed 6 months of regular hemodialysis therapy. Their results showed that between months 1 and 6 there were statistically significant increases in predialysis serum albumin, iron, transferrin saturation, creatinine, and the normalized protein equivalent of total nitrogen appearance (nPNA). Body weight declined initially until month 4 and then started to increase. There was a strong curvilinear relationship between the mean nPNA and the final serum albumin concentration achieved. They thus conclude that following the initiation of hemodialysis, there is an overall improvement in nutritional status that includes an increase in dietary protein intake (as measured by nPNA) and that the improvement in nutritional status may be related to this increase in dietary protein intake likely afforded by the relief of uraemic symptomatology by hemodialysis. The second study by Drs Pupim, Kent, Caglar, Shyr, Hakim, and Ikizler from Vanderbilt University Medical Center studied 50 incident hemodialysis patients at baseline and then every 3 months following the initiation of hemodialysis up to 1 year.2Pupim LB Kent P Caglar K Shyr Y Hakim RM Ikizler TA Improvement in nutritional parameters after initiation of chronic hemodialysis.Am J Kidney Dis. 2002; 40: 143-151Abstract Full Text Full Text PDF Scopus (61) Google Scholar They followed multiple nutritional markers including biochemical parameters as well as analysis of body composition by bioimpedance (BIA) and dual energy x-ray absorptiometry (DEXA); the latter being done only at baseline and at 12 months. Their results showed that at baseline the nutritional markers were well correlated among each other. Following the initiation of hemodialysis, there were marked improvements in most of the nutritional parameters, including serum albumin, serum prealbumin, nPNA, BIA, and DEXA-derived fat mass and BIA-derived reactance and phase angle, suggesting improvements in cellular health. The improvement in nutritional parameters was influenced by baseline nutritional status to the extent that even at the 12-month follow-up, the baseline nutritional parameters predicted the final study values. Their conclusions were also that initiation of maintenance hemodialysis therapy is associated with improvement in most of the nutritional markers. They point out that the nutritional benefits of the increased solute clearance provided by hemodialysis overruled its potential catabolic effects. An important finding was that the extent of improvement was dependent on the nutritional status at the time of initiation of dialysis. The two studies are very similar. They are virtually identical in study concept. The study patients had somewhat different demographic characteristics from the two areas: there being fewer African-American and more diabetic patients in the UCLA study. The Vanderbilt study examined more variables including body composition and also measured C-reactive protein (CRP) as an indicator of inflammation. The UCLA study1Mehrotra R Berman N Alistwani A Kopple JD Improvement of nutritional status after initiation of maintenance hemodialysis.Am J Kidney Dis. 2002; 40: 133-142Abstract Full Text Full Text PDF Scopus (72) Google Scholar invoked some very sophisticated statistical methodologies looking at slopes of change (eg, albumin) and the interrelations between various parameters such as albumin and nPNA. Nevertheless, the results can clearly be put together and create one story, namely that following the initiation of dialysis, the serum albumin will start to rise. To what extent it rises will depend on the age of the patient (the elderly being disadvantaged) and on the improvement of dietary protein intake as measured by nPNA. The nPNA is not influenced by catabolism as the CRP levels found by the Vanderbilt study2Pupim LB Kent P Caglar K Shyr Y Hakim RM Ikizler TA Improvement in nutritional parameters after initiation of chronic hemodialysis.Am J Kidney Dis. 2002; 40: 143-151Abstract Full Text Full Text PDF Scopus (61) Google Scholar were no different from beginning to end, and all analyses for trends in nutritional markers were reported following adjustments for CRP. The nPNA improvement plus other nutritional parameters were also independent of both residual renal function and any decrease in urinary protein losses from baseline over study time. Both studies showed an initial loss in body weight. The UCLA study1Mehrotra R Berman N Alistwani A Kopple JD Improvement of nutritional status after initiation of maintenance hemodialysis.Am J Kidney Dis. 2002; 40: 133-142Abstract Full Text Full Text PDF Scopus (72) Google Scholar surmised that this could be dependent on change in extracellular fluid volume from the initiation of dialysis. The Vanderbilt study2Pupim LB Kent P Caglar K Shyr Y Hakim RM Ikizler TA Improvement in nutritional parameters after initiation of chronic hemodialysis.Am J Kidney Dis. 2002; 40: 143-151Abstract Full Text Full Text PDF Scopus (61) Google Scholar confirms this by BIA. The UCLA study1Mehrotra R Berman N Alistwani A Kopple JD Improvement of nutritional status after initiation of maintenance hemodialysis.Am J Kidney Dis. 2002; 40: 133-142Abstract Full Text Full Text PDF Scopus (72) Google Scholar shows the trend to increase weight following the fourth month, which was felt due to an increase in lean body mass and, hence, might account for the increase in serum creatinine. The Vanderbilt study2Pupim LB Kent P Caglar K Shyr Y Hakim RM Ikizler TA Improvement in nutritional parameters after initiation of chronic hemodialysis.Am J Kidney Dis. 2002; 40: 143-151Abstract Full Text Full Text PDF Scopus (61) Google Scholar showed any increase in body weight to come after the ninth month, and this was not associated with DEXA evidence of increase in lean body mass but rather of fat content. The Vanderbilt team2Pupim LB Kent P Caglar K Shyr Y Hakim RM Ikizler TA Improvement in nutritional parameters after initiation of chronic hemodialysis.Am J Kidney Dis. 2002; 40: 143-151Abstract Full Text Full Text PDF Scopus (61) Google Scholar surmised that the increase in creatinine might be at least in part a reflection of the loss of renal function over time and that more studies were indicated in this area. The most important contribution of the UCLA paper1Mehrotra R Berman N Alistwani A Kopple JD Improvement of nutritional status after initiation of maintenance hemodialysis.Am J Kidney Dis. 2002; 40: 133-142Abstract Full Text Full Text PDF Scopus (72) Google Scholar is to point out the strong relationship between the mean nPNA (ie, dietary intake) following commencement of dialysis and the final serum albumin. The major contribution from the Vanderbilt study2Pupim LB Kent P Caglar K Shyr Y Hakim RM Ikizler TA Improvement in nutritional parameters after initiation of chronic hemodialysis.Am J Kidney Dis. 2002; 40: 143-151Abstract Full Text Full Text PDF Scopus (61) Google Scholar is to show that limitations on improvement relate to how poorly nourished the patient was at baseline. These two studies certainly point out that protein energy malnutrition is common in the predialysis patient and strongly suggest that the malnutrition has the potential for reversal following the commencement of dialysis therapy. The improvement that does take place is most likely due to the reversal of uremic toxicity and improvement in dietary protein and energy intake afforded by appetite improvement. The message given by the studies is that hemodialysis should be instituted before significant malnutrition takes place, especially so in the elderly, who are more likely to have poorer nutritional parameters at the initiation of dialysis and who respond less favorably to the dialysis therapy. Both of these studies are limited by the fact that they are observational in nature and are not randomized controlled studies. However, how can one do a randomized controlled study on the effect of dialysis initiation on nutritional status? Such a study would be likely unethical and certainly fraught with problems of defining the characteristics of a group to start dialysis where it is still safe to leave a control malnourished group for (say) a further 6-month period without dialysis. Do these studies, therefore, support the concept of the “early start” for dialysis therapy? They likely do, but how early and for who—all or only the malnourished? The Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD),9Korevaar JC Jansen MAM Dekker FW for the Netherlands Cooperative Study on the Adequacy of Dialysis Study Group et al.When to initiate dialysis: Effect of proposed US guidelines on survival.Lancet. 2001; 358: 1046-1050Abstract Full Text Full Text PDF Scopus (187) Google Scholar a large multicenter prospective cohort (not randomized) study showed that “timely” starters on dialysis by NKF-K/DOQI standards (ie, weekly Kt/V urea at start is greater than 2.0 or if less than 2.0, then nPNA is above 0.8 g/kg/d and body mass index is at least 20 kg/m2) had a small gain in survival time in the first 3 years after the start of dialysis over “late” starters. This gain, however, was felt to be purely a reflection of initiating dialysis earlier in the disease and the study did not identify the nPNA at dialysis initiation as influencing survival odds.9Korevaar JC Jansen MAM Dekker FW for the Netherlands Cooperative Study on the Adequacy of Dialysis Study Group et al.When to initiate dialysis: Effect of proposed US guidelines on survival.Lancet. 2001; 358: 1046-1050Abstract Full Text Full Text PDF Scopus (187) Google Scholar Perhaps only a randomized study with both malnourished and well-nourished patients at dialysis initiation will help. A North American randomized controlled study was considered to examine the influence of “early start” on longer term survival but following a pilot study was deemed to be impossible on logistical grounds (Churchill and Clase, personal communication). Such a study has, however, been started in Australia and New Zealand. This trial has the acronym IDEAL (Initiating Dialysis Early and Late) and, while powered for mortality, has several secondary endpoints and includes nutritional and morbidity substudies (C. Pollock, personal communication). We await those results with interest. These studies also bring back the concept that the dialysis treatment itself may have significant influence on nutritional parameters and, hence, on outcome. While this may be turning the clock back a whole decade and reopen the “nPNA/Kt/V controversy” intuitively, one has to believe that the adequacy of dialysis delivered and how it is delivered (high flux, low flux, peritoneal dialysis, hemodialysis, etc) has some influence upon dietary protein intake at least in protein malnourished uremic patients without the “malnutrition, inflammation, atherosclerosis” syndrome.10Efendic E Lindholm B Bergstrom J Stenvinkel P Strong association between malnutrition, inflammation and atherosclerosis in chronic renal failure.Kidney Int. 1999; 55: 1899-1911Google Scholar We now know the preliminary results of the HEMO study as far as survival is concerned. The secondary analyses of that study regarding dose and flux on nutritional parameters are also eagerly awaited. Until further information regarding nutrition, early start, dose, and flux is obtained, these current studies certainly give credence to the NKF-K/DOQI recommendations on the initiation of dialysis therapy on malnourished patients with advanced chronic renal failure in whom other interventions have failed to result in nutritional improvement.7National Kidney Foundation/Kidney-Dialysis Outcome Quality Initiative Clinical Practice Guidelines for nutrition in chronic renal failure.Am J Kidney Dis. 2000; 35: S1-S140Google Scholar