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over the past 20 years , children receiving dialysis have benefited not only from advances in modern technology , but also from improvements in clinical management .
nevertheless , conventional haemodialysis performed three times a week still results in an increased risk of cardiovascular morbidity and impaired growth in children [ 1 , 2 ] .
study   found that the prescription of a high urea dialysis dose in hemodialysis performed three times a week in adults failed to result in an improvement in clinical outcome .
therefore ,  a complete dialysis dose  should be prescribed , that is , not only a urea dialysis dose ( a small solute diffusive clearance )   but also a convective dialysis volume ( middle molecule uremic toxin clearance ) . at present , despite great interest and feasibility , hemodiafiltration is rarely performed [ 68 ] . however , the case for performing intensified and/or more frequent hemodialysis regimens in both children [ 913 ] and adults has been put forward [ 1417 ] .
all intensified treatment modalities , ranging from daily procedures to long intermittent hemodialysis sessions , clearly improve patient outcome in terms of mortality and morbidity . in children , daily on - line hemodiafiltration has even been found to promote catch - up growth [ 9 , 18 ] .
however , intensive and daily dialysis is rarely performed as a long - term dialysis regimen for  all patients  as it is often only considered as a rescue therapy .
  urea kinetic modeling is generally accepted as a method for evaluating the dialysis dose prescribed , despite the fact that it is of limited value in the assessment of dialysis adequacy .
quantification of dialysis is based on a urea dialysis dose , that is , kt / v , ( dialyzer urea clearance ( k ) multiplied by duration ( t ) of the dialysis session and divided by urea volume ( v ) of distribution . on -
line urea clearance measurements , which are currently available on modern dialysis machines , make it easy to calculate the dialysis dose ( kt ) and , thus , allow the clinician to calculate the kt / v for each session , providing an estimation of v which is assumed to be equal to the total body water .
impedancemetry   is of clinical interest when estimating v , as it does not require blood sampling to be performed .
however , it does require the use and availability of a specific machine ( bcm , fresenius medical care ) .
the use of anthropometric formulas to calculate  v  has been found to be less accurate especially in children .
an indirect method of calculating  v  can be achieved using the ratio kt / kt / v , where kt is obtained from the ionic dialysance provided by the dialysis monitor , and kt / v is obtained from the second generation of daugirdas formula , which requires blood samples to be taken before and after the dialysis session .
the on - line urea kt / v assessment performed by the dialysis monitor gives out a single pool kt / v ( spkt / v ) , with a proposed target dose of 1.4 per dialysis session in anuric patients [ 19 , 21 ] .
therefore , formulas for estimating the equilibrated kt / v ( ekt / v ) are available [ 4 , 19 , 21 ] . due to the need for postdialytic blood sampling , in practice
spkt / v is a clinically acceptable way of monitoring hd adequacy , at least in a thrice - weekly hemodialysis regimen . in cases where hemodialysis is performed more frequently , standard kt / v ( stkt / v )
this formula integrates spkt / v and ekt / v in order to account for urea peaks and valleys .  
a dialysis dose based on body surface area ( san - stkt / v ) has been suggested to be a more accurate way of determining the urea dialysis dose required in children : a dose over 2.45   should be considered to be an optimal dialysis dose , promoting catch up statural growth in children on chronic dialysis .
nevertheless , a complete dialysis dose   should be preferred to an urea dialysis dose ,  only  a diffusive dialysis dose .
complete dialysis dose  is difficult to define and stays under discussion [ 4 , 5 ] : beside the urea dialysis dose , a diffusive dialysis dose ,   a convective dialysis dose could be proposed [ 6 , 15 , 24 ] , based on phosphate dialytic removal and on the achieved beta 2 microglobulinemia .
  uremic toxins can be categorized into three groups : free water soluble low - molecular - weight solutes such as urea , middle - sized solutes such as beta 2 microglobulin ( 2 m ) , and protein - bound solutes such as p - cresol acid .
free  as it is surrounded by water molecules ; therefore , it has a clearance profile similar to that of the middle - sized molecules . the removal of uremic toxins by dialysis relies upon a combination of the diffusion process , convective mass transport , and membrane adsorption .
haemodialysis ( hd ) provides optimal removal of low - molecular - weight uremic toxins such as urea due to the diffusive flow of solutes .
conversely , the convective flow of solutes which mainly occurs in hemofiltration ( hf ) and hemodiafiltration ( hdf ) results in the removal of middle - sized and large molecules .
convection and diffusion are presented as two separate phenomena , but in practice they are on a continuous interference .
nevertheless , the concept of a complete dialysis dose , which includes not only a urea dialysis dose , that is , kt / v urea , but also a convective dialysis dose , that is , the convective volume achieved per dialysis session , may be of importance in terms of patient outcome  in particular resulting in an improvement in cardiovascular mortality [ 6 , 26 ] .   
hemodiafiltration is a combination of hd and hf performed during the same procedure , allowing a determined convective flow per dialysis session .
the weight loss that arises when hd occurs only ensures a convective flow equal to the ultrafiltration rate , that is , a small convective volume . during conventional hd with high - flux filters ,  internal 
hdf occurs due to back filtration of the dialysate , providing only a slightly larger but nondetermined convective volume .
moreover , the dialysate used is not always a sterile , nonpyrogenic substitution fluid , and therefore may provoke systemic inflammation [ 28 , 29 ] .
altogether , on - line hemodiafiltration , that is , substitution fluid prepared from ultrafiltration of the ultrapure dialysate , which is a safe routine replacement therapy [ 6 , 7 , 17 , 30 , 31 ] , enables the use of a determined high convective volume throughout the dialysis session , impacting on both solute removal and clinical outcome .
hdf offers improved control of phosphate when compared to both hd and high - flux hd [ 6 , 7 ] .
predialysis 2 m serum levels are decreased during ol - hdf ; the 2 m dialytic removal correlates with the convective volume achieved .
high - efficiency hdf , as defined in adult patients in postdilution mode using a convective dose of more than 15 
l per session , is superior to low - efficiency hdf both in terms of solute removal and patient outcome [ 6 , 7 ] .
as demonstrated by a recent single centre study , when performed on a daily basis , on - line hdf using a convective volume in pre dilution mode of 18 to 27  l / m per procedure even promotes catch up growth in children . at present
, it is not known if the different intensive hemodialysis regimens available are equivalent in terms of their growth promoting capacity [ 11 , 21 ] .
  the purity , in terms of microbial contaminants measured as colony forming units ( cfu ) and endotoxins units ( eu ) , is recorded for the different fluids used in the dialysis procedure .  
the purity should be carefully assessed in order to limit the risk of patient 's systemic inflammation , in the clinical setting illustrated by the surrogate parameter of an elevated crp .
standard quality dialysis fluid ( bacterial count < 100  cfu / ml ; endotoxin units < 0.50  eu / ml ) is not appropriate for use with high - flux filters for hd , due to the internal convective flow , that is , the backfiltration .
high - flux membranes require the use of ultrapure dialysate , that is , bacterial count < 0.1  cfu / ml ; endotoxin count < 0.05  ui / ml . for  at risk
 patients , the current european guidelines recommend the use of highly permeable membranes in hd .
  repeated conventional dialysis sessions have an additive effect which contributes , towards the cardiovascular risk profile in children , that is , morbidity and mortality .
adverse effects related to dialysis include : high blood pressure , left ventricular hypertrophy or impaired left ventricular function , elevated calcium / phosphate resulting in calcification of blood vessels ( particularly vascular / coronnary calcifications ) , and systemic inflammation .
the above list accounts for the vast majority of dialysis related risks to the cardiovascular system , contributing towards increased morbidity and mortality [ 2 , 32 ] .    in children on chronic conventional hemodialysis
for example , 79% of children on hd in the united states have an elevated bp at the start of the dialysis session .
a further study found that left ventricular hypertrophy ( lvh ) was worryingly common ( 82% of patients ) in children at the initiation of dialysis , and remained frequent ( 82% ) and severe ( 59% ) after 2 years of maintenance conventional hemodialysis .   
in children on conventional hd , lvh may be improved   by optimizing the sodium balance , for example , by strict dietary control of sodium intake , dry weight achievement , and supplementary dialysis time .
overall however , intensified hemodialysis regimens should not be disregarded in the hope of improving cardiovascular health , and they should , therefore , not be considered exclusively as rescue therapy .
however , they are not only malnourished  which infers that dietary supplementation would be curative , but they are also cachexic ( i.e. , in a state of protein loss ) .
malnutrition and cachexia combined are two important factors which contribute towards the protein wasting seen in uremic patients .  
conventional hemodialysis performed three times a week requires patients to stick to a restrictive diet which limits the intake of protein , water , sodium , potassium , and phosphate , whilst at the same time maintaining an adequate calorie intake . due to limited uremic toxin removal
, chelators of phosphate and potassium are often prescribed- but these are also factors which contribute towards anorexia , that is , malnutrition .
conversely , if the dialysed child has a good appetite , he is at risk of increased weight gain between dialysis sessions and of raised blood phosphate or potassium levels and of major metabolic acidosis . in such circumstances ,
the duration of the dialysis procedure is often increased from 4 to 5 hours , and sometimes an additional dialysis session later in the week may be required .
the child on long - term dialysis often considers these changes or adaptions to be a form of punishment , and he responds in turn by fasting and becoming increasingly less compliant and more opposed to the procedure . aside from malnutrition , protein catabolism is an independent factor which plays a major role in the muscle wasting and poor linear growth that result despite rh gh therapy .
loss of protein stores , that is , more cachexia than malnutrition   is a multifactorial event , caused by : inflammation   , acidosis , uremic toxin retention , and volume overload , that is , poor blood pressure control .
interesting , on - line hdf performed on a daily basis has been found to reverse both cachexia and malnutrition and to promote catch up growth in children .
  in children , an adequate hemodialysis prescription requires more than simply a urea dialysis dose ( table 1 ) .
if economically feasible , high - flux membranes should be used in combination with ultrapure disposable dialysate .
on - line hemodiafiltration , that is , substitution fluid prepared from ultrafiltration of the ultrapure dialysate , is a safe routine replacement therapy which has a positive impact not only on the removal of solutes such as phosphate or 2 m , but also on clinical outcome .
intensified and more frequent hemodialysis regimens , that is , high - flux hd or on - line hdf ,   provide adequate hemodialysis in children , and should , therefore , not exclusively be used as rescue therapy .
nevertheless , in young children with renal residual clearance , peritoneal dialysis remains an excellent choice of chronic at home dialysis modality .
when prescribing hemodialysis in children , the clinician should first establish an adequate regimen , before seeking to optimize the treatment ( fischbach et al . 
 2005 ) . 
 a complete dialysis dose should consist of a urea dialysis dose and a determined convective volume . 
 intensified and more frequent dialysis regimens should not be considered exclusively as rescue therapy . 
 interestingly , a recent single - center study demonstrated that frequent on - line hdf provides an optimal dialysis prescription , both in terms of blood pressure control ( and therefore avoidance of left ventricular hypertrophy ) , and catch - up growth , that is , no malnutrition or cachexia and less resistance to growth hormone . 
 nevertheless , this one - center experience would benefit from a prospective randomized study .