Peritoneal protein loss (PPL) through peritoneal effluent has been a well-recognized detrimental result of peritoneal dialysis (PD) treatment since its inception. Investigation has focused mainly on PPL quantitative and qualitative determinations and evaluation of its prognostic value.
A comprehensive review of the pathophysiology of PPL (3-pore model revisited), methods of quantification, dialysate protein composition, and impact on clinical outcomes is presented herein. The author summarizes a brief analysis of associated cardiovascular disease and nutritional consequences, exploring the controversial cause-effect on mortality and technique failure.
Therapeutic modalities aiming to reduce PPL (angiotensin-converting enzyme inhibitors [ACEI]s and vitamin D therapies) were explored, although it is unclear whether PPL represents a valid therapeutic target or, on the other hand, is solely a manifestation of endothelial dysfunction.
BasturkT., UnsalA., KocY., NezaketE., AhbapE., SakaciT.The effects of angiotensin-converting enzyme inhibitors on peritoneal protein loss and solute transport in peritoneal dialysis patients.Clinics2012; 67(8): 877–83.
TjiongH.L., ZijlstraF.J., RietveldT., WattimenaJ.L., HuijmansJ.G.M., SwartG.R.Peritoneal protein losses and cytokine generation in automated peritoneal dialysis with combined amino acids and glucose solutions.Mediat Inflamm2007; 2007: 97272.
4.
DulaneyJ.T., HatchF.E.JrPeritoneal dialysis and loss of proteins: a review.Kidney Int1984; 26(3): 253–62.
Sanchez-VillanuevaR., BajoA., del PesoG., Fernandez-Reyes, GonzálezE., RomeroS.Higher daily peritoneal protein clearance when initiating peritoneal dialysis is independently associated with peripheral arterial disease (PAD): a possible new marker of systemic endothelial dysfunction?Nephrol Dial Transplant2009; 24: 1009–14.
7.
DongJ., ChenY., LuoS., XuR., XuY.Peritoneal protein leakage, systemic inflammation, and peritonitis risk in patients on peritoneal dialysis.Perit Dial Int2013; 33: 273–9.
8.
HaraldssonB.Assessing the peritoneal dialysis capacities of individual patients.Kidney Int1995; 47: 1187–98.
9.
Pérez-FontánM., Rodríguez-CarmonaA., BarredaD., López MuñizA., Blanco CastroN., García FalcónT.Peritoneal protein transport during the baseline peritoneal equilibration test is an accurate predictor of the outcome of peritoneal dialysis patients.Nephron Clin Pract2010; 116: c104–13.
10.
RippeB.A three-pore model of peritoneal transport.Perit Dial Int1993; 13(2): 35–8.
11.
RippeB., DaviesS.Permeability of peritoneal and glomerular capillaries: what are the differences according to pore theory?Perit Dial Int2011; 31: 249–58.
12.
BalafaO., HalbesmaN., StruijkD.G., DekkerF.W., KredietR.T.Peritoneal albumin and protein losses do not predict outcome in peritoneal dialysis patients.Clin J Am Soc Nephrol2011; 6: 561–6.
13.
ArbeiterK., StembergerR., GreenbaumL., MüllerT., KonstantinA., HerknerK.Peritoneal transport kinetics of proteins in children on chronic peritoneal dialysis.Perit Dial Int2003; 23: 162–8.
14.
HaraldssonB., EkholmC., RippeB.Importance of molecular charge for the passage of endogenous macromolecules across continuous capillary walls, studied by serum clearance of lactate dehydrogenase (LDH) isoenzymes.Acta Physiol Scand1983; 117: 123–30.
15.
AdamsonR.H., HuxleyV.H., CurryF.E.Single capillary permeability to proteins having similar size but different charge.Am J Physiol1988; 254: H304–12.
16.
AsgeirssonD., AxelssonJ., RippeC., RippeB.Similarity of permeabilities for Ficoll, pullulan, charge-modified albumin and native albumin across the rat peritoneal membrane.Acta Physiol (Oxf)2009; 196: 427–33.
17.
CurryF.R.Microvascular solute and water transport.Microcirculation2005; 12: 17–31.
18.
RippeB., VenturoliD., SimonsenO., de ArteagaJ.Fluid and electrolyte transport across the peritoneal membrane during CAPD according to the three-pore model.Perit Dial Int2004; 24: 10–27.
19.
KredietR.T.Chapter 6: The physiology of peritoneal solute, water and lymphatic transport. In: KhannaR., KredietR.T., eds. Nolph and Gokal's Textbook of peritoneal dialysis, 3rd edition.New York, NY: Springer, 2009: 137–72.
20.
TangY., ZhongH., DiaoY., QinM., ZhouX.Peritoneal transport rate, systemic inflammation, and residual renal function determine peritoneal protein clearance in continuous ambulatory peritoneal dialysis patients.Int Urol Nephrol2014; 46(11): 2215–9.
21.
HeafJ.G., SaracS., AfzalS.A high peritoneal large pore fluid flux causes hypoalbuminemia and is a risk factor for death in peritoneal dialysis patients.Nephrol Dial Transplant2005; 20: 2194–201.
22.
SzetoC.C., ChowK.M., LamC.W., CheungR., KwanB.C., ChungK.Y.Peritoneal albumin excretion is a strong predictor of cardiovascular events in peritoneal dialysis patients: a prospective cohort study.Perit Dial Int2005; 25: 445–52.
23.
CoronelF., CigarránS., HerreroJ.A.Peritoneal protein losses in diabetic patients starting peritoneal dialysis: is there a relationship with diabetic vascular lesions?Adv Perit Dial2009; 25: 115–8.
24.
ElsurerR., AfsarB., SezerS., OzdemirF.N., HaberalM.Peritoneal albumin leakage: 2-year prospective cardiovascular event occurrence and patient survival analysis.Nephrology (Carlton)2009; 14: 712–5.
25.
GomesA.M., Pérez FontánM., Rodríguez-CarmonaA., López-MuñizA., FernándezM., PeteiroJ.Peritoneal total protein transport assessed from peritoneal equilibration tests with different dialysate glucose concentrations.Perit Dial Int2010; 30: 549–57.
26.
TamA.C., LapworthR.Biochemical analysis of pleural fluid: what should we measure?Ann Clin Biochem38(4): 311–22.
27.
PerlJ., HuckvaleK., ChellarM., JohnB., DaviesS.J.Peritoneal protein clearance and not peritoneal membrane transport status predicts survival in a contemporary cohort of peritoneal dialysis patients.Clin J Am Soc Nephrol2009; 4: 1201–6.
28.
JerónimoT., Malho GuedesA., Del PesoG., SilvaA.P., SelgasR., BajoM.A.Paricalcitol and peritoneal protein loss in PD—a double-center study.Blood Purif2018; 46(2): 103–10.
29.
RajakarunaG., CaplinB., DavenportA.Peritoneal protein clearance rather than faster transport status determines outcomes in peritoneal dialysis patients.Perit Dial Int2015; 35: 216–21.
LambE.J., MacKenzieF., StevensP.E.How should proteinuria be detected and measured?Ann Clin Bioch46(3): 205–17.
32.
WangH., TianY., ChienC., KanW., LiaoP., WuH.Differential proteomic characterization between normal peritoneal fluid and diabetic peritoneal dialysate.Nephrol Dial Transplant (2010) 25: 1955–63.
33.
BrewisI.A., TopleyN.Proteomics and peritoneal dialysis: early days but clear potential.Nephrol Dial Transplant2010; 25: 1749–53.
34.
BrimbleK.S., WalkerM., MargettsP.J., KundhalK., RabbatC.Meta-analysis: peritoneal membrane transport, mortality, and technique failure in peritoneal dialysis.J Am Soc Nephrol2006; 17: 2591–8.
35.
YangX., FangW., BargmanJ.M., OreopoulosD.G.High peritoneal permeability is not associated with higher mortality or technique failure in patients on automated peritoneal dialysis.Perit Dial Int2008; 28: 82–92.
36.
CuccuruloM., EvangelistaC., VilasiA., SimeoniM., AvellaF., RiccioL.Proteomic analysis of peritoneal fluid of patients treated by peritoneal dialysis: effect of glucose concentration.Nephrol Dial Transplant2011; 26: 1990–9.
37.
ChangT.I., KangE.W., LeeY.K., ShinS.K.Higher peritoneal protein clearance as a risk factor for cardiovascular disease in peritoneal dialysis patient.2013. PLOS One8(2): e56223.
38.
Van BiesenW., Van der TolA., VeysN., DequidtC., LameireN., VanholderR.The personal dialysis capacity test is superior to the peritoneal equilibration test to discriminate inflammation as the cause of fast transport status in peritoneal dialysis patients.Clin J Am Soc Nephrol2006; 1: 269–74.
39.
WeirM.R.Microalbuminuria and cardiovascular disease.Clin J Am Soc Nephrol2007; 2: 581–90.
40.
SzetoC.C., ChowK.M., ChungK.Y., KwanB.C., LiP.K.Peritoneal protein and albumin excretion as markers of cardiovascular risk factor and systemic endothelial dysfunction.Hong Kong J Nephrol2004; 6: 31–7.
41.
KaysenG.A.Meta-analysis: biological basis of hypoalbuminaemia in ESRD.J Am Soc Nephrol1998; 9: 2368–76.
42.
IkizlerT.A., GreeneJ.H., WingardR.L., ParkerR.A., HakimR.M.Spontaneous dietary protein intake during progression of chronic renal failure.J Am Soc Nephrol1995; 6(5): 1386–91.
43.
KathuriaP., MooreH.L., KhannaR., TwardowskiZ., GoelS., NolphK.Effect of dialysis modality and membrane transport characteristics on dialysate protein losses of patients on peritoneal dialysis.Perit Dial Int1997; 17: 449–54.
44.
KangD.H., YoonK.I., ChoiK.B., LeeR., LeeH.Y., HanD.S.Relationship of peritoneal membrane transport characteristics to the nutritional status in CAPD patients.Nephrol Dial Transplant1999; 14: 1715–22.
45.
SzetoC.C., LawM.C., WongT.Y., LeungC.B., LiP.K.Peritoneal transport status correlates with morbidity but not longitudinal change of nutritional status of continuous ambulatory peritoneal dialysis patients: a 2-year prospective study.Am J Kidney Dis2001; 37: 329–36.
46.
ChungS.H., HeimburgerO., StenvinkelP., WangT., LindholmB.Influence of peritoneal transport rate, inflammation, and fluid removal on nutritional status and clinical outcome in prevalent peritoneal dialysis patients.Perit Dial Int2003; 23(2): 174–83.
47.
HartyJ.C., BoultonH., VenningM.C., GokalR.Is peritoneal permeability an adverse risk factor for malnutrition in CAPD patients?Miner Electrolyte Metab1996; 22(1-3): 97–101.
48.
DombrosN., DratwaM., FerianiM., GokalR., HeimburgerO., KredietR.EBPG Expert Group on Peritoneal Dialysis. European best practice guidelines for peritoneal dialysis. 8 Nutrition in peritoneal dialysis.Nephrol Dial Transplant2005; 20(Suppl 9): ix28–33.
NolphK.D., SorkinM., RubinJ., ArfaniaD., ProwantB., FrutoL.Continuous ambulatory peritoneal dialysis: three-year experience at one center.Ann Intern Med1980; 92(5): 609–13.
51.
GordonS., RubiniM.E.Protein losses during peritoneal dialysis.Am J Med Sci1967; 257: 283–92.
52.
DelmezJ.A., SlatopolskyE., MartinK.J., GearingB.N., HarterH.R.Minerals, vitamin D, and parathyroid hormone in continuous ambulatory peritoneal dialysis.Kidney Int1982; 21: 862–7.
53.
ChanM.K., BaillodR.A., VargheseZ., SweenyP., MoorheadJ.F.Immunoglobulins and complement components (C3, C4) in CAPD and hemodialysis patients.Dialysis Transplant1983; 12: 777–8.
54.
RobeyC., ShreedharK., BatumanV.Effects of chronic peritoneal dialysis on thyroid function tests.Am J Kidney Dis1989; 13(2): 99–103.
55.
NgY.Y., WuS.C., Da LinH., HuA.H., HouC.C., ChouY.Y.Prevalence of clinical and subclinical thyroid disease in a peritoneal dialysis population.Perit Dial Int2012; (1): 86–93.
56.
KaganA., ZadikZ., GertlerA., UlmanM., Bar-KhayimY.Serum concentrations and peritoneal loss of growth hormone and growth-hormone-binding protein activity in older adults undergoing continuous ambulatory peritoneal dialysis: comparison with haemodialysis patients and normal subjects.Nephrol Dial Transplant1993; 8: 352–6.
BajoM.A., SelgasR., del PesoG., CastroM.J., HeviaC., GilF.Use of icodextrin for diurnal exchange in patients undergoing automatic peritoneal dialysis. Comparison with glucose solutions.Nefrologia2002; 22(4): 384–55.
59.
YoungG.A., DibbleJ.B., TaylorA.E., KendallS., BrownjohnA.M.A longitudinal study of the effects of amino acid-based CAPD fluid on amino acid retention and protein losses.Nephrol Dial Transplant1989; 4(10): 900–5.
60.
NakamotoH., ImaiH., FukushimaR., IshidaY., YamanouchiY., SuzukiH.Role of the renin-angiotensin system in the pathogenesis of peritoneal fibrosis.Perit Dial Int2008; 28(3): 83–7.
BraunN., FritzP., BieggerD., KimmelM., ReimoldF., UlmerC.Difference in the expression of hormone receptors and fibrotic markers in the human peritoneum—implications for therapeutic targets to prevent encapsulating peritoneal sclerosis.Perit Dial Int2011; 31: 291–300.
63.
Sánchez-ÁlvarezJ.E., Rodriguez-SuarezC., Coronel-AguilarD., González-DiázI., Núñez- MoralM., Peláez-RequejoB.Paricalcitol reduces proteinuria but does not modify peritoneal protein loss in patients on peritoneal dialysis.Nefrologia2013; 33: 70–6.
64.
PimentelA., Malho GuedesA., CavaleiroP., JerónimoT., LaranjoC., BernardoI.The role of cinacalcet in peritoneal dwells: changes in PET.Nephrol Dial Transplant2017; 32(Suppl 3): iii303–4.
65.
SjølandJ.A., PedersenR.S., JespersenJ., GramJ.Intraperitoneal heparin reduces peritoneal permeability and increases ultrafiltration in peritoneal dialysis patients.Nephrol Dial Transplant2004; 19: 1264–8.
