A need for a paradigm shift in focus: From Kt/V_urea to appropriate removal of sodium (the ignored uremic toxin)

Abstract

Hemodialysis for chronic renal failure was introduced and developed in Seattle, WA, in the 1960s. Using Kiil dialyzers, weekly dialysis time and frequency were established to be about 30 hours on 3 time weekly dialysis. This dialysis time and frequency was associated with 10% yearly mortality in the United States in 1970s. Later in 1970s, newer and more efficient dialyzers were developed and it was felt that dialysis time could be shortened. An additional incentive to shorten dialysis was felt to be lower cost and higher convenience. Additional support for shortening dialysis time was provided by a randomized prospective trial performed by National Cooperative Dialysis Study (NCDS). This study committed a Type II statistical error rejecting the time of dialysis as an important factor in determining the quality of dialysis. This study also provided the basis for the establishment of the Kt/Vurea index as a measure of dialysis adequacy. This index having been established in a sacrosanct randomized controlled trial (RCT), was readily accepted by the HD community, and led to shorter dialysis, and higher mortality in the United States. Kt/Vurea is a poor measure of dialysis quality because it combines three unrelated variables into a single formula. These variables influence the clinical status of the patient independent of each other. It is impossible to compensate short dialysis duration (t) with the increased clearance of urea (K), because the tolerance of ultrafiltration depends on the plasma‐refilling rate, which has nothing in common with urea clearance. Later, another RCT (the HEMO study) committed a Type III statistical error by asking the wrong research question, thus not yielding any valuable results. Fortunately, it did not lead to deterioration of dialysis outcomes in the United States. The third RCT in this field (“in‐center hemodialysis 6 times per week versus 3 times per week”) did not bring forth any valuable results, but at least confirmed what was already known. The fourth such trial (“The effects of frequent nocturnal home hemodialysis”) too did not show any positive results primarily due to significant subject recruitment issues leading to inappropriate selection of patients. Comparison of the value of peritoneal dialysis and HD in RCTs could not be completed because of recruitment problems. Randomized controlled trials have therefore failed to yield any meaningful information in the area of dose and or frequency of hemodialysis.

Forty‐five years on home hemodialysis, a case of exceptional longevity

“…6,17 Unresolved dispute of intensified dialysis is whether frequency is the pivotal element for better care, or rather, time on dialysis is the largest independent variable to affirm clinical success. [18][19][20] HHD prescription evolved over time to prescriptions consistent with the limitations of the platforms used. 21,22 One concern of frequent hemodialysis is the damage to the access wall and endothelium due to frequent cannulation.…”

“…Observational studies are suggestive of a commensurate improvement of the survival, as well, though good quality, randomized trials are still lacking . Unresolved dispute of intensified dialysis is whether frequency is the pivotal element for better care, or rather, time on dialysis is the largest independent variable to affirm clinical success . HHD prescription evolved over time to prescriptions consistent with the limitations of the platforms used …”

Dialysis adequacy reconsidered: The person comes first

“…Chief among these are its failure to measure middle molecule clearance and to meaningfully distinguish between the separate effects of time spent on dialysis and clearance, inaccuracy in select groups of patients (e.g., at the extremes of body mass index), lack of a standardized approach to measurement, and failure to address volume management. [5][6][7][8][9][10] Despite widespread recognition of the importance of delivering an adequate dialysis dose within the nephrology community and improvements over time in the provision of dialysis, mortality rates for patients on dialysis remain extremely high. Clinical trials in this area-which have been limited by inadequate power, reliance on surrogate markers, and failure to include outcome measures that matter to patients-have failed to show a clear and consistent benefit of increasing Kt/V above the minimum threshold level recommended in clinical practice guidelines or of increasing dialysis session length or frequency.…”

The association of overhydration with chronic inflammation in chronic maintenance hemodiafiltration patients

“…From the very beginning of the dialysis era, the founding fathers of chronic hemodialysis, including Belding H. Scribner, emphasized the fact that adequate hemodialysis should be able to control the volume and adequate time should be allocated to dialysis treatments to facilitate this . Somehow, however, this call was left unheeded . As treatment times were shortened, hemodialysis adequacy was interpreted as analogous with small molecular clearance and volume control and treatment time became overlooked parameters of hemodialysis quality .…”

“…Somehow, however, this call was left unheeded . As treatment times were shortened, hemodialysis adequacy was interpreted as analogous with small molecular clearance and volume control and treatment time became overlooked parameters of hemodialysis quality . At present and parallel with high mortality, the hemodialysis population is plagued with complications arising from inadequate volume control including resistant hypertension, left ventricular hypertrophy, hemodynamic instability related to high ultrafiltration rates and very high cardiovascular complication rates, among others.…”