Clinical Benefits of Low-glucose Peritoneal Dialysis Fluid Regimens Combined Solution Regimens


Because both dwells with icodextrin and amino acid solutions reduce glucose exposure to the peritoneal membrane, it is obvious that a PD regimen containing only those solutions may provide a PD strategy without glucose exposure at all. Unfortunately, owing to the characteristics of icodextrin, with its slow but extended ultrafiltration profile,14


use in clinical practice is limited to once daily


for the long dwell, although there is limited proof of improved ultrafiltration with two exchanges a day.65,66


Amino acid-based


solutions can be used only once a day because they have limited ultrafiltration capacity,48 metabolic acidosis.67,68


and more frequent use may induce Nevertheless, in PD strategies in which these


solutions replace glucose-based solutions, the daily glucose exposure of the peritoneal membrane should be decreased, potentially resulting in less peritoneal damage. So far, only limited data on such regimens are available. Le Poole et al.69


demonstrated


in a cross-over design that a PD regimen combining icodextrin, an amino acid solution and lactate–bicarbonate-buffered glucose solution contained fewer advanced glycation end-products70


and


resulted in a substantial decrease in intraperitoneal glucose loads (94.6 ± 57.4 g/24 hours versus 159.8 ± 49.1 g/24 hours),71 be a clinically safe PD strategy.69,72


proving to Such a PD regimen resulted in


similar body weights, blood pressure, decline in urine volume, residual creatinine clearance and laboratory measurements to the standard PD regimen containing only the standard glucose-based solutions.69


Pentosidine in the albumin fraction tended to be lower during the low-glucose regimen.71


Better preservation of the


mesothelium was found on the one hand, but signs of increased peritoneal activation during physioneal, extraneal and nutrineal (PEN) treatment were seen on the other hand.73


In addition, a rise in


effluent vascular endothelial growth factor (VEGF) levels was observed, which could not be attributed to glucose and GDP loads.73


in which the effects of this regimen are studied in diabetic patients, will clarify this issue further. The study examines whether a low-glucose PD regime improves glycaemic control and other metabolic parameters in diabetic CAPD and APD patients compared with a glucose-only PD therapy regimen and will report in mid-2012.


Altogether, these observations make it impossible to conclude firmly at present whether the use of a low-glucose CAPD regimen, in which biocompatible glucose-based solutions, amino acid-based solutions and icodextrin are combined, brings additional clinical benefits. The findings of the recently completed PEN versus Dianeal only improved metabolic control in diabetic CAPD and APD patients (IMPENDIA) study,74


Whereas this regimen also resulted in less exposure to glucose breakdown products, its effects on systemic levels of glucose breakdown products and advanced glycation end-products was unexpected: higher levels of methylglyoxal and CML but lower levels of 3-deoxyglucosone and N(ε)-(carboxyethyl)lysine were found.71


the treatment modalities full-time (i.e. to haemodialysis in case of peritonitis or to CAPD for the holidays) was an additional practical advantage. Further research is necessary before recommending more widely the benefits of this combined strategy in incident end-stage renal disease patients.75


More frequently, the addition of haemodialysis


therapy has been applied in prevalent PD patients with ultrafiltration failure or after loss of residual renal function. In both cases, PD can only be maintained by increasing the concentration and/or frequency of the dwells, resulting in increased glucose exposure to the peritoneal membrane and most probably enhancing peritoneal membrane damage. In such cases, adding haemodialysis sessions to the PD regimen will reduce the need for such increased glucose exposure, making it feasible for patients to remain longer on PD therapy,77,78


which


is often preferred by patients from a lifestyle perspective but may also be preferred because of the continuous nature of PD treatment instead of the intermittent nature of standard haemodialysis. Another way to achieve reduction in glucose-induced peritoneal damage in this respect is to alternate between PD only and haemodialysis only for longer periods. During the haemodialysis period, the peritoneal membrane might partially recover. Indeed, it could be demonstrated in rats that the glucose-induced damage of the peritoneal membrane regressed after withdrawal of exposure of glucose to the peritoneal membrane.79


So far,


there are no analogous human data available. Altogether, it can be concluded that combining haemodialysis with PD may have advantages and be appropriate in certain patient categories. However, additional research clearly showing the benefit of such a combined dialysis strategy needs to be performed before advocating it as an important treatment modality.


Concluding Remarks


Without doubt, the glucose and GDPs in the standard PD solutions contribute to peritoneal damage, ultimately resulting in ultrafiltration failure and, subsequently, in technique failure; in the majority of patients, application of PD regimens containing less glucose is a rational strategy. Study results now emerging indicate that the use of icodextrin, replacing glucose for the long dwell, seems to be associated with improved technique44,46 patient survival.44,45


and acid-based solutions are applied.60,64


To date, this has not been seen when amino The minimum exposure of


glucose and GDPs to the peritoneal membrane can be achieved with a PD regimen combining icodextrin, amino acid-based solution and the newer biocompatible glucose-based solutions. Although such a regimen appears to be clinically safe for a relatively long period,72


for cardiovascular outcomes are inconsistent.71,73


data from effluent and systemic markers Thus further


Peritoneal Dialysis and Haemodialysis A completely different strategy aiming to avoid or reduce glucose exposure-induced damage of the peritoneal membrane is combining haemodialysis with PD; it has been eloquently reviewed by Kawanishi and McIntyre.75


studies on this topic are warranted to demonstrate a benefit for such a PD strategy. Support for this regimen will be obtained when the results from the recently completed IMPENDIA study are released. Recent reports on the use of biocompatible glucose-based solutions indicate that those solutions may result in better ultrafiltration80,81 reduced mortality,82–84


and their use appears to be associated with although this has recently been challenged.85


So far, this has only been studied in incident patients.76 In this study, combined use of these dialysis modalities for one year with two PD exchanges per day and two haemodialysis sessions per week resulted in preservation of residual renal function, with adequate dialytic clearance of small solutes, good metabolic control and a reduction in left ventricular mass. The possibility of switching between


EUROPEAN NEPHROLOGY


Thus at present the best strategy to prevent ultrafiltration and technique failure, as well as mortality, might be a PD strategy combining these newer biocompatible glucose-based solutions with icodextrin to reduce glucose- and GDP-induced peritoneal and systemic damage. Combining such a PD strategy with alternating periods of haemodialysis may further prolong PD technique survival and reduce mortality, but this approach needs further investigation. n


51


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