Portal de Periódicos da CAPES

Fluid overload and residual renal function in peritoneal dialysis: the proof of the pudding is in the eating

2013; Elsevier BV; Volume: 85; Issue: 1 Linguagem: Inglês

10.1038/ki.2013.298

1523-1755

Wim Van Biesen, Achim Jörres,

Thermoregulation and physiological responses

McCafferty and colleagues report on a retrospective analysis in peritoneal dialysis patients in whom fluid status was assessed by multifrequency bioimpedance. During 12 months of follow-up, overhydration, as identified by an increased ratio of extracellular over total body water, was not associated with better preservation of residual renal function (RRF). These findings suggest that running patients 'wet' might not contribute to better preservation of RRF in peritoneal dialysis. McCafferty and colleagues report on a retrospective analysis in peritoneal dialysis patients in whom fluid status was assessed by multifrequency bioimpedance. During 12 months of follow-up, overhydration, as identified by an increased ratio of extracellular over total body water, was not associated with better preservation of residual renal function (RRF). These findings suggest that running patients 'wet' might not contribute to better preservation of RRF in peritoneal dialysis. Since the reanalysis of the data of the Canada–USA (CANUSA) Peritoneal Dialysis Study Group it has been acknowledged that there is an important association between residual renal function (RRF) and survival in patients on peritoneal dialysis. This association is strongest when RRF is expressed as urinary output rather than as small-solute clearance,1.Bargman J.M. Thorpe K.E. Churchill D.N. Relative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: a reanalysis of the CANUSA study.J Am Soc Nephrol. 2001; 12: 2158-2162PubMed Google Scholar suggesting that preservation of a good hydration balance is more important than clearance.2.Van Biesen W. Lameire N. Verbeke F. et al.Residual renal function and volume status in peritoneal dialysis patients: a conflict of interest?.J Nephrol. 2008; 21: 299-304PubMed Google Scholar Some nephrologists have taken this as an excuse to leave their patients overhydrated rather than risking episodes of hypovolemia and hypotension that may promote the loss of RRF. Such strategy, however, may result in more hypertension, left ventricular hypertrophy, and, ultimately, excess cardiovascular mortality. Moreover, it neglects the possibility that RRF is associated with better survival because it allows better maintenance of volume status. So far, clear evidence from interventional trials is lacking that hypervolemia as compared with euvolemia or hypovolemia may lead to better preservation of RRF. In fact, earlier observational studies did not find an association between overhydration and better RRF, even after adjusting for other potential confounders such as diabetic status, age, and gender.3.Van Biesen W. Williams J.D. Covic A.C. et al.Fluid status in peritoneal dialysis patients: the European Body Composition Monitoring (EuroBCM) study cohort.PLoS One [online]. 2011; 6: e17148Crossref PubMed Scopus (195) Google Scholar McCafferty et al.4.McCafferty K. Fan S. Davenport A. Extracellular volume expansion, measured by multifrequency bioimpedance, does not help preserve residual renal function in peritoneal dialysis patients.Kidney Int. 2013; 85: 151-157Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar (this issue) report a retrospective analysis in peritoneal dialysis patients in whom fluid status was assessed by multifrequency bioimpedance and who were followed for at least 12 months. The authors conclude that an increased ratio of extracellular over total body water (ECW/TBW) was not associated with preservation of RRF. Overall, their results appear to lend further support to the notion that, at least in peritoneal dialysis patients, better preservation of RRF cannot be achieved by running the patients 'wet.' Certain interpretations of the study may require a note of caution. The study evaluated only prevalent patients, which may make it likely that patients with a faster decline of RRF to anuria were not included. Although there was no statistically significant difference, median peritoneal dialysis vintage was double in the lowest versus the highest tertile of overhydration, indeed pointing to 'survival of the fittest.' In addition, the requirement of a 12-month follow-up may further promote a negative selection bias for patients with a faster decline of RRF, or a negative clinical course leading to death or to technical failure of peritoneal dialysis and transfer to hemodialysis. Moreover, as in other cohort studies,3.Van Biesen W. Williams J.D. Covic A.C. et al.Fluid status in peritoneal dialysis patients: the European Body Composition Monitoring (EuroBCM) study cohort.PLoS One [online]. 2011; 6: e17148Crossref PubMed Scopus (195) Google Scholar the overhydrated patients were more likely to be diabetic and had worse glycemic control. It has been demonstrated that less tight glycemic control enhances microvascular damage, especially in the kidney. So there might have been substantial baseline differences between the different overhydration tertiles that not only may explain the overhydration, but may also have contributed to a decline of RRF. Another problem, often inherent to observational studies of hydration status, is that there was only one baseline measurement in these patients, and no standardized intervention to reduce overhydration or protocol on how the volume overload was managed. As a consequence, there is no information on whether these patients were intentionally left fluid overloaded, or whether attempts were made to correct overhydration. Either of these courses could have influenced the evolution of RRF. In fact, it has been demonstrated that the same intervention to reduce overhydration can lead to either preservation or deterioration of RRF, depending on the original hydration status of the patient.5.Davies S.J. Woodrow G. Donovan K. et al.Icodextrin improves the fluid status of peritoneal dialysis patients: results of a double-blind randomized controlled trial.J Am Soc Nephrol. 2003; 14: 2338-2344Crossref PubMed Scopus (306) Google Scholar,6.Konings C.J. Kooman J.P. Gladziwa U. et al.A decline in residual glomerular filtration during the use of icodextrin may be due to underhydration.Kidney Int. 2005; 67: 1190-1191Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar Notably, in the study by McCafferty et al.,4.McCafferty K. Fan S. Davenport A. Extracellular volume expansion, measured by multifrequency bioimpedance, does not help preserve residual renal function in peritoneal dialysis patients.Kidney Int. 2013; 85: 151-157Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar more patients in the overhydration group were receiving loop diuretics and spironolactone, indicating that they may already have been overhydrated. Besides issues related to the observational and retrospective character of the analyses, some other points need to be considered in interpreting results of studies using bioimpedance for the assessment of fluid status. In the study by McCafferty et al.,4.McCafferty K. Fan S. Davenport A. Extracellular volume expansion, measured by multifrequency bioimpedance, does not help preserve residual renal function in peritoneal dialysis patients.Kidney Int. 2013; 85: 151-157Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar overhydration was expressed as ECW/TBW ratio. An increase in ECW/TBW ratio can, however, result either from excess fluid in the intercellular compartment (that is, tissue edema and thus true overhydration), or from a decrease in intracellular water, hinting at malnutrition. The latter may seem likely in the present study, as overhydrated patients had not only lower serum albumin levels but also lower cholesterol and creatinine levels. As a close association exists between malnutrition and inflammation, and between inflammation and deterioration of RRF, it remains unclear to what extent inflammation may have contributed to both overhydration and the deterioration of RRF in the present study. One important issue remains underemphasized in this study: the important relation between fluid and salt intake and the need for more use of hypertonic peritoneal dialysis solutions to achieve or maintain fluid status. Both a high salt intake and the use of hypertonic glucose3.Van Biesen W. Williams J.D. Covic A.C. et al.Fluid status in peritoneal dialysis patients: the European Body Composition Monitoring (EuroBCM) study cohort.PLoS One [online]. 2011; 6: e17148Crossref PubMed Scopus (195) Google Scholar have been associated with hypervolemia, though the latter probably reflects attempts to correct preexistent hypervolemia. However, these factors are also associated with a more rapid decline of RRF7.Cianciaruso B. Bellizzi V. Minutolo R. et al.Salt intake and renal outcome in patients with progressive renal disease.Miner Electrolyte Metab. 1988; 24: 296-301Crossref Scopus (137) Google Scholar and a faster deterioration of peritoneal membrane function.8.Davies S.J. Phillips L. Naish P.F. et al.Peritoneal glucose exposure and changes in membrane solute transport with time on peritoneal dialysis.J Am Soc Nephrol. 2001; 12: 1046-1051PubMed Google Scholar There is little doubt that achievement of an optimal volume status is an important parameter of adequacy of dialysis, but several important questions remain to be answered. First, it is still unclear how we should evaluate 'hydration status.' Obviously clinical evaluation is mandatory, but it is probably too insensitive a parameter. Edema is a late sign of volume overload, and blood pressure can be misleading when there is either hypertension (due to either volume overload or vascular stiffness) or hypotension (due to either volume depletion or congestive heart failure). Multifrequency bioimpedance is becoming increasingly popular as an easy-to-use and reproducible method for the assessment of volume status. However, it remains to be determined to what extent the results obtained by different devices and methods are comparable, as is also apparent in the study of McCafferty and colleagues.4.McCafferty K. Fan S. Davenport A. Extracellular volume expansion, measured by multifrequency bioimpedance, does not help preserve residual renal function in peritoneal dialysis patients.Kidney Int. 2013; 85: 151-157Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar Consequently, only devices and algorithms that were validated in the appropriate patient population should be used. A major argument in favor of bioimpedance techniques is that they may be used to assess tissue overhydration, which in peritoneal dialysis patients is a more frequent problem than an excess of extracellular fluid volume, which can readily be assessed by ultrasound or chest X-ray. Second, and most important, it is still a matter of debate how to achieve and maintain fluid status in patients undergoing peritoneal dialysis. So far, it has never been properly explored in a randomized controlled trial whether the use of diuretics, the restriction of salt and water intake, the use of hypertonic glucose, or other strategies are the optimal approach to achieve or maintain an appropriate fluid balance. Finally, it is unclear how we should express or measure RRF: as volume output (diuresis), the most likely reason why RRF improves outcome, or as solute clearance? We believe the individual patient's treatment plan for peritoneal dialysis (Figure 1) should at least encompass: the avoidance of hypertonic glucose exchanges; application of the appropriate intraperitoneal dwell time for the respective peritoneal membrane transport type;9.van Biesen W. Heimburger O. Krediet R. et al.Evaluation of peritoneal membrane characteristics: clinical advice for prescription management by the ERBP working group.Nephrol Dial Transplant. 2010; 25: 2052-2062Crossref PubMed Scopus (77) Google Scholar and a moderate dietary restriction of salt and water intake. The results of the recently published balANZ trial10.Johnson D.W. Brown F.G. Clarke M. et al.Effects of biocompatible versus standard fluid on peritoneal dialysis outcomes.J Am Soc Nephrol. 2012; 23: 1097-1107Crossref PubMed Scopus (158) Google Scholar might indicate that the use of biocompatible peritoneal dialysis fluids containing low concentrations of glucose-degradation products may play an additional role in the preservation of both RRF and peritoneal membrane integrity. On the other hand, the potential benefits of icodextrin in augmenting peritoneal ultrafiltration must be tempered by the observation that icodextrin usage may risk hypovolemia, so possibly risking loss of RRF.6.Konings C.J. Kooman J.P. Gladziwa U. et al.A decline in residual glomerular filtration during the use of icodextrin may be due to underhydration.Kidney Int. 2005; 67: 1190-1191Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar Finally, as with most treatment paradigms in clinical practice, the proof of the pudding is in the eating. At the end of the day, prospective randomized controlled trials will be needed to confirm that the proposed strategy not only is intuitively attractive, but will actually lead to improved patient outcomes. However, in view of the different combinations of interventions to be tested, such a randomized controlled trial might not be realistic. A prospective observational cohort study, where the outcome of different treatment strategies is followed, might be a more realistic and achievable design.