14  Peritoneal Dialysis Solutions

 lternate PD Solutions
A
and Membrane-Sparing Strategies

241

These studies suggest a potential role for
L-carnitine-containing dialysis solutions as a
membrane-preserving strategy and/or to prevent
or treat carnitine deficiency, but further data is
required on long-term safety and efficacy. No
pediatric data exists, and no commercial
L-carnitine-containing solution is yet available.

Carnitine  Carnitine is a water-soluble molecule
important in fatty acid metabolism. Depletion of
muscle and plasma-free carnitine may occur in
patients on PD due to losses of carnitine in the dialysate, resulting in elevation of acylcarnitine and an
elevated acyl/free carnitine ratio. Adult patients on Dialysis Solutions with Dissolved Molecular
APD have lower carnitine levels than their CAPD Hydrogen (H2)  Molecular hydrogen (H2) has
counterparts [131]. Dialysis-related carnitine disor- been shown to have antioxidant and anti-­
der may be associated with erythropoietin-­ inflammatory properties. PDS can be loaded
stimulating agent (ESA) resistance, hypotension, with H2 by placing the bag in H2-enriched
abnormal lipid metabolism, and muscle weakness. electrolyzed water. In rats, PDS with infused
Carnitine can be supplemented by the IV or intra- H2 has been shown to induce less peritoneal
peritoneal (IP) route [131, 132]. Oral carnitine is damage than the same PDS alone [139]. In a
considered contraindicated in patients on dialysis 2-week study in six prevalent Japanese patients,
due to potential accumulation of trimethylamine H2-infused PDS was clinically well tolerated,
produced by metabolism of carnitine by gut bacte- with a trend toward improvement in effluent

ria [133], although there is published data on CA125 and mesothelin in some patients [140].
improvement in plasma carnitine levels [134, 135] More clinical experience is obviously required
and apolipoprotein B levels [136] in children on with this novel therapy. Additionally, H2 is
rapidly lost from the PDS upon exposure to air,
PD supplemented with oral carnitine.
despite wrapping the bags in foil, so significant
A study in rats showed that L-carnitine exerts logistical considerations must be overcome
an osmotic effect similar to glucose, with half the before this could become commercially
water transport facilitated by aquaporin-1 water available.
channels [137]. The same authors conducted a 5day study in four adults on CAPD. A solution of Polyglucose Solutions  Polydispersity is the
1.5% glucose and 0.25% L-carnitine as the over- ratio of weight-average molecular weight (Mw)
night dwell yielded higher ultrafiltration than to number-average molecular weight (Mn), while
with a 2.5% glucose solution and similar uremic ultrafiltration efficiency is the ratio of UF to carsolute removal [137]. Plasma carnitine levels bohydrate absorbed. Icodextrin, with a polydisrose substantially and were not in steady state by persity of 2.6, has superior UF efficiency
5  days, although the percent absorption from compared to glucose when used over a long
each dwell fell progressively, with increasing dwell. Based on theoretical considerations using
the three-pore peritoneal model, alternate soluamounts recovered from the dialysate each day.
A further 4-month randomized study of insu- tions to icodextrin to provide sustained UF have
lin sensitivity was done in 27 adult patients on been explored. Experimental studies in rabbits
CAPD (15 carnitine, 12 glucose group) using a have shown that polyglucose solutions with low
single exchange of a solution of either 2.5% or polydispersity are effective osmotic agents [141].
1.5% glucose with 0.1% carnitine added, with A 6 K polymer solution with a Mw of 6.4 kilodaltwo glucose exchanges and an overnight icodex- tons (KDa) and polydispersity of 2.3 was comtrin exchange. Compared to the control group pared to a 19 K polymer solution with a Mw of
who received three glucose exchanges and the 18.8 kDa and polydispersity of 2.0. The 6 K soluovernight icodextrin exchange, the L-carnitine tion was associated with greater UF and superior
group showed improved insulin sensitivity and UF efficiency but at the expense of more absorption of the polymer. Further rabbit studies by the
preserved urine volume [138].


E. Harvey

242


same authors have shown that an 11% glucose
polymer solution with a Mw of 18–19 kDa and a
polydispersity of 2 provides higher UF without
greater carbohydrate absorption [142]. These initial studies suggest that altering both the molecular weight distribution and the concentration of
glucose polymers can provide prolonged UF
without increased carbohydrate absorption.
These solutions are not yet commercially
available.
Hyperbranched Polyglycerol  Hyperbranched
polyglycerol (HPG) is a hydrophilic, nontoxic,
non-immunogenic, water-soluble branched polyether polymer, which is being used in many biomedical applications. It has limited accumulation
in internal organs after intravenous injection,
although may accumulate in the reticuloendothelial system with repeated exposure. It does not
activate platelets or the coagulation or complement systems. HPG-based PD solutions have
been produced with concentrations varying from
2.5% to 15%, osmolality of 294–424 mOsm/kg,
and neutral pH of 6.6–7.4. In a rat PD model utilizing a single exchange, HPG PD solutions produced equal or superior solute and fluid removal
and were associated with less damage to the peritoneal membrane histologically [143] as compared to cPDS.

6-month conversion of the PEN group to
Dianeal™. The studies measured multiple peritoneal markers of inflammation and demonstrated
an improvement in urine volume in the PEN
group and increased levels of anti-fibrotic markers and adiponectin and an associated reduction
in some inflammatory markers in the PEN group,
suggesting better preservation of peritoneal
membrane integrity [146] [98]. However, a significant flaw was the absence of peritoneal morphology to corroborate improved membrane
integrity.
Two other studies have shown this regimen to
be well tolerated clinically but with a suggestion
of increased deaths in diabetic patients [147].

There is no published pediatric experience with
this regimen.

Conclusion

Misra et al. suggest that the ideal biocompatible
solution must provide sustained ultrafiltration
and solute clearance; have no adverse effects and
have potential nutritional or metabolic benefits if
absorbed; be associated with no interference with
peritoneal host defenses; and cause no peritoneal
inflammation or long-term peritoneal damage
[9]. Despite significant advances in the knowlIn a 3-month study in rats, HPG PDS was edge of the beneficial and detrimental effects of
associated with stable blood chemistry, with less peritoneal dialysis, the ideal PDS does not yet
peritoneal membrane structural change and neo-­ exist. In pediatrics, prescription of PD is further
angiogenesis, and with less upregulation of confounded by varying requirements based on
inflammatory pathways, as compared with cPDS age, size, and growth, along with regional
[144].
differences in delivery systems and solution
­
The kinetics of HPG in uremia must be further availability.
elucidated. HPG solutions have theoretical
PDSs should be considered “drugs” and
advantage and may compete with icodextrin as a ordered with knowledge of their composition,
single daily exchange in the future, but much risks, and potential benefits. The decision to use a
more clinical experience is required [145].
particular PDS is a complex one based on what is
available to the clinician in their region of pracPEN Study  The PEN study compared a regimen tice, the delivery system (cycler versus CAPD),
of
Physioneal™

(1–2
exchanges/day), and a determination of the most appropriate conExtraneal™ (1 overnight exchange), and tent of buffer, calcium, osmotic agent, and magNutrineal™ (1 exchange daily) compared to 3–4 nesium. An ideal solution may not exist for an
exchanges of Dianeal™ daily in incident adult individual patient, requiring additional medical
PD patients over 12  months, followed by a therapy to maintain homeostasis.


14  Peritoneal Dialysis Solutions

In general, for children, recommendations are
to use neutral pH and low GDP biocompatible
solutions; to minimize exposure to hypertonic
glucose; to use a buffer which will correct acidosis without causing alkalosis; and to utilize membrane sparing strategies which may include the
use of icodextrin, amino acid solutions, or newer
osmotic agents [2, 45, 54].
In pediatrics, a “one size fits all” strategy will
not be successful. Thus, a pediatric program must
have a variety of solutions with varying buffer
type and concentration, a variety of osmotic
agents, and variable calcium concentrations to
meet the needs of the majority of pediatric PD
patients.

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