Prognostic Value of Transport Status

The peritoneal transport characteristics dictate the efficiency of the biological membrane for solute clearance and UF.  Peritoneal transport is a dynamic parameter that often changes in time and requires regular monitoring¹.  In matching the prescription to the patent’s needs, knowledge of transport characteristics are essential.

A trend towards increased peritoneal transport with time has been observed.  The etiology of these changes is probably multi-factorial.  Among the possible causes for this increased transport are peritonitis, diabetes mellitus, dialysate glucose, glucose degradation products (GDPs), advanced glycation end-products (AGEs), acidic pH and plasticizers and others. 

Peritoneal Transport and Time

The prevalence of morphological changes in the peritoneal membrane increases with time on PD.  The most distinctive histologic changes are reduplication of the basal lamina, interstitial fibrosis, vascular hyalinization and neoangiogenesis^2,3.  Williams et al. examined the morphologic features of the peritoneal membrane of 130 patients undergoing peritoneal dialysis and compared them with membranes of normal individuals, uremic pre-dialysis patients and patients undergoing hemodialysis.  They observed a progressively higher percentage of vasculopathy on PD patients with time on dialysis. 

Prevalence of Vasculopathy

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Increased peritoneal membrane transport has been considered a significant risk factor and reported to be associated with decreased patient and technique survival^4,5.  High transport provides higher clearances (K).  Higher K, while improving solute removal are also associated with mortality enhancing effects or processes⁶.  We know that higher peritoneal membrane transport as measured by the 4 hour D/D₀ for glucose or the D/P_cr  is associated with lower serum albumin concentration^7-12.  Higher D/P_cr is associated with higher K_p all else being equal.  It is very difficult to define the interdependence between serum albumin and high peritoneal transport as adverse predictors in PD patients since the two variables are very strongly correlated. 

Peritoneal transport rates depend on both effective peritoneal surface area and the intrinsic permeability of peritoneal capillaries.  While the former may be at least partly related to BSA, the determinants of the latter are less well understood.  Blake offers the possibility that sicker, malnourished patients simply have more permeable capillaries as is the case with critically ill patients with adult respiratory distress syndrome⁸.  If that is the case, malnutrition and low SAC would be expected to be present prior to the commencement of PD.  Harty et al. found no difference in dietary protein intake, protein catabolic rate, serum transferrin levels or lean body mass and peritoneal transport status¹³.  However, Nolph et al. reported significantly lower protein catabolic rate and lean body mass by creatinine kinetics in high transporters¹⁴.  We must also consider the possibility that both hypoalbuminemia and high peritoneal transport status result from a state of chronic inflammation or increase in cytokine regulation in the uremic patient as previously supported by Lowrie’s data¹⁵ and by Kaysen et al. who showed that serum albumin concentration in hemodialysis patients is strongly influenced by its role as an inverse acute phase reactant¹⁶.

References:

1. Davies SJ, Bryan J, Phillips L, Russell GI. Longitudinal changes in peritoneal kinetics: the effects of peritoneal dialysis and peritonitis. Nephrol Dial Transplant 11:498-506, 1996
2. Nakayama M, Kawaguchi Y, Yamada K, Hasegawa T, Takazoe K, Katoh N, Hayakawa H, Osaka N, Yamamoto H, Ogawa A, Kubo H, Shigematsu T, Sakai O, Horiuchi S. Immunohistochemical detection of advanced glycosylation end-products in the peritoneum and its possible pathophysiological role in CAPD. Kidney Int 51:182-186, 1997
3. Williams JD, Craig KJ, Topley N, Von Ruhland C, Fallon M, Newman GR, Mackenzie RK, Williams GT. Morphologic changes in the peritoneal membrane of patients with renal disease. J Am Soc Nephrol 13:470-479, 2002
4. Churchill DN, Thorpe KE, Nolph KD, Keshaviah PR, Oreopoulos DG, Pagé D. Increased peritoneal membrane transport is associated with decreased patient and technique survival for continuous peritoneal dialysis patients. J Am Soc Nephrol 9:1285-1292, 1998
5. Davies SJ, Phillips L, Russell GI. Peritoneal solute transport predicts survival on CAPD independently of residual renal function. Nephrol Dial Transplant 13:962-968, 1998
6. Diaz-Buxo JA, Lowrie EG, Lew NL, Zhang H, Zhu X, Lazarus JM. Associates of mortality among peritoneal dialysis patients with special reference to peritoneal transport rates and solute clearance. Am J Kidney Dis 33:523-534, 1999
7. Lowrie EG, Huang WH, Lew NL. Death risk predictors among peritoneal dialysis and hemodialysis patients:  A preliminary comparison. Am J Kidney Dis 26:220-228, 1995
8. Blake PG. What is the problem with high transporters? Perit Dial Int 17:317-320, 1997
9. Nolph KD, Khanna R, Twardowski ZJ, Moore HL. Predictors of serum albumin concentration (SA) in CAPD. J Am Soc Nephrol 3:416(Abstract), 1992
10. Malhotra D, Tzamaloukas AH, Murata GH, Fox L, Goldman RS, Avasthi PS. Serum albumin in continuous peritoneal dialysis:  Its predictors and relationship to urea clearance. Kidney Int 50:243-249, 1996
11. Díaz-Alvarenga A, Abasta-Jimenez M, Bravo B, Gamba G, Correa-Rotter R. Serum albumin and body surface area are the strongest predictors of the peritoneal transport type, In: Khanna R (ed.): Advances in Peritoneal Dialysis, Toronto, Canada, Multimed, Inc., 1994, pp 47-51.
12. Cueto-Manzano AM, Espinosa A, Hernández A, Correa-Rotter R. Peritoneal transport kinetics correlate with serum albumin but not with the overall nutritional status in CAPD patients. Am J Kidney Dis 30:229-236, 1997
13. Harty JC, Boulton H, Venning MC, Gokal R. Is peritoneal permeability an adverse risk factor for malnutrition in CAPD patients? Miner Electrolyte Metab 22:97-101, 1996
14. Nolph KD, Moore HL, Prowant B, Twardowski ZJ, Khanna R, Gamboa S, Keshaviah P. Continuous ambulatory peritoneal dialysis with a high flux membrane. ASAIO J 39:904-909, 1993
15. Lowrie EG.  Conceptual model for a core pathobiology of uremia with special reference to anemia, malnourishment and mortality among dialysis patients.  Seminars in Dialysis 10:115-129, 1997
16. Kaysen GA, Rathore V, Shearer GC, Depner TA. Mechanisms of hypoalbuminemia in hemodialysis patients. Kidney Int 48:510-517, 1995