Dialysis


process where rate of removal = clearance x solute concentration (R = K x C). It may appear that one may use any of the three parameters for quantifying dialysis. However ‘R’ is determined by ‘G’, the solute generation rate which at a steady state must equal ‘R’. This implies that K and C are inversely related and either could be measured for quantification of dialysis efficiency. However, the problem with measuring C (and not K) is due to the fact that G, not included in the above relationship, independently affects C, the blood urea nitrogen (BUN) concentration. The measurement of clearance, K, avoids this confusion.


Owing to the very nature of the process, HD is most efficient in the first 60–90 minutes. As the solute concentration falls, the concentration gradient, the main driving force for diffusion, falls, resulting in a decline in rate of removal (even though the total amount of solute removed with time increases). It is apparent that the ratio of R/C, i.e. the clearance K, does not change during dialysis. The decline in the concentration of BUN during HD is logarithmic and not linear; therefore there is a decline in dialysis efficiency with time for small solutes. For larger solutes, the solute gradient is maintained for a longer time and enhancing time on dialysis helps in removal of such solutes.


Larger solutes are primarily cleared by convective removal, which occurs when UF is performed. UF resulting in convective removal is dependent on the transmembrane pressure (TMP) across the membrane (net difference of hydrostatic pressure and oncotic pressure in the blood compartment and hydrostatic pressure in the dialysate compartment). Mathematically, the total solute flux by


convection, JC = Q f.S where Q f represents the UF rate, and S is the sieving coefficient of solute.


The importance of larger molecular weight substances in causing dialysis morbidity and mortality is being increasingly recognized. An efficient dialysis session is like a ‘flash in the pan’ with rapid solute removal during dialysis followed by steady rise of solute levels, i.e. BUN, in the interdialytic period, such that the time average solute concentration (TAC) over a defined time period remains higher than desired. Moreover, the time average deviation (TAD), a measure of fluctuation around the TAC, also remains high, highlighting the ‘unphysiology’ of three-times-a-week dialysis. More frequent and/or longer dialysis, on the other hand, is more efficient (lower TAC) and more physiologic (lower TAD). Therefore, it is not surprising that more frequent dialysis not only provides a higher dose of dialysis in terms of small solute removal (larger number of more efficient segments) but also improves clearance of higher molecular weight solutes by the nature of the process itself.


Why Did We Need a Number?


During the 1960s and 1970s dialysis was prescribed solely based on clinical signs and symptoms, with prescriptions varying in time and number of sessions, ranging from three to 36 hours a week. In 1975, a conference on the concept of adequacy was held in Monterey, California, to study the issue of ‘dose of dialysis.’ This led to the National Cooperative Dialysis Study (NCDS), a randomized controlled trial using urea as a prototype for ‘small solute’ and treatment time as a surrogate for middle molecule (MM).4


The trial was stopped early because of higher mortality in the high BUN group (odds ~5.0) and the short time 66 group (odds ~1.5).7


However, the effect of treatment time was ignored, owing to being statistically insignificant at (p<0.06), leading Chertow et al. to remark that “one might argue that the NCDS session length, p=0.06 was the most ‘significant’ (important), ‘non-significant’ (statistical) effect in the history of dialysis research”.8


A secondary analysis of the NCDS concluded that there is a four-fold increase in


probability of ‘clinical failure’ for all patients with (single-pool) spKt/Vurea <0.8 (where K is clearance, t is dialysis time and Vurea is volume distribution of urea) compared with patients with spKt/Vurea of 0.9–1.62.9 In 1997, the National Kidney Foundation (NKF)–Dialysis Outcomes


Quality Initiative (DOQI) modeled the dialysis adequacy to a Kt/Vurea of 1.2 for three-times-a-week HD. The Kt/V was further modified by


Daugirdas by incorporating the effect of UF and the effect of residual renal function.10


Issues with Single-pool Kt/Vurea The use of Kt/V as an index for adequacy of dialysis3


has been


questioned. The use of non-equilibrated urea in the Kt/V equation overestimates urea reduction resulting in overestimation of dialysis dose. Wide variations exist in the prescribed HD regimens among patients. To overcome this, a continuous clearance equivalent of adequacy was proposed ‘standard Kt/V’.11


Scaling of Kt to an


appropriate variable also remains an issue. Data suggest that association between dialysis dose and survival varies across demographic groups and is possibly attributed to erroneous calculations due to variations in V.12,13


For example, females have lower


V compared with males and hence the ratio Kt/V will show a higher value, resulting in under-dialysis.


Similar issues with V may be encountered in small patients. Some alternative methods of scaling Kt (other than V) have been proposed. The concept of scaling Kt using anthropometrically derived body surface area (BSA) has been suggested by Daugirdas et al.14


Since V:BSA is about


15% different in men than in women (BSA in women is 15% higher), if the dialysis dose is scaled to BSA, women will receive 15% less dialysis. In their analysis they concluded that rescaling Kt to BSA would obligate more HD for women and smaller patients and less dialysis for larger, male patients.


Morton and Singer have tried to answer the fundamental question of the ‘nature of the relationship’ between glomerular filtration rate (GFR) and V and whether filtration rate should be normalized to a parameter other than V.15


Comparative data in a large mammalian species suggest that the GFR changes in parallel to basal metabolic rate (BMR). According to Morton et al. examination of comparative physiology of allometric scaling as it relates to renal function indicates that changes in GFR between species are non-linear and are governed by an allometric equation given by:


Y = axb


where Y is GFR, a is scaling coefficient, x is body mass, and b is the power coefficient (0.77).15


This is why a man with a mass of 70kg and a GFR of 120ml/minute requires almost twice the GFR of a horse with mass of 500kg and a GFR


US NEPHROLOGY


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