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Peritoneal Dialysis

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PreserveUpgrade to Comprehensive PD

Prolong

Protect Preserve

P3

7

Protect, Preserve, Prolong – working together to improve survival

At Fresenius Medical Care, we work continuously to improve peritoneal dialysis treatment and therapy. Our work has been validated by numerous studies demonstrating the benefits and advantages of our products, devices and software. The P3 programme allows you to provide your patients with a therapy that Protects, Preserves and Prolongs their time on PD.

To learn more about the P3 categories Protect and Prolong please contact your local sales representative.

The P3 programme is available only from Fresenius Medical Care.

P3

balance improves patient survival

Cum

. Sur

viva

l

1.0

0.8

0.6

0.4

0.2

0.0

balance

conventional PD fluid

0 1 2 3 4Survival (years)

Kaplan-Meier plot of patient survival1, 2

Chart adapted from Lee et al.1,2

p < 0.0001

AP office: Fresenius Medical Care Asia-Pacific Limited · 51/F Sun Hung Kai Centre · 30 Harbour Road · Wanchai · Hong Kong · Tel: +(852) 2802 2900 · Fax: +(852) 2898 2273

www.fmc-asia.com

Information balance

Excipients: Water for injections, hydrochloric acid, sodium hydroxide, sodium hydrogen carbonate. Indications: End-stage (decompensated) chronic renal failure of any origin treated with peritoneal dialysis. Contraindications: Solution related: Solutions with 1.5%/2.3%/4.25% glucose, 1.75 mmol/l calcium: Severe hypokalaemia and severe hypercalcaemia. Solutions with 1.5%/2.3%/4.25% glucose, 1.25 mmol/l calcium: Severe hypokalaemia and severe hypocalcaemia. Solutions with 4.25% glucose: Additionally hypovolaemia and arterial hypotension. Treatment related: Recent abdominal surgery or injury, burns, hernia, inflammatory abdominal skin reaction (dermatitis), inflammatory bowel diseases (Crohn’s disease, ulcerative colitis, diverticulitis), peritonitis, non-healing weeping wounds (abdominal fistulae), intra-abdominal tumours, intestinal obstruction (ileus), lung diseases (especially pneumonia), metabolic disorders (lactic acidosis), generalised blood poisoning (sepsis), extreme weight loss (cachexia), particularly when adequate nutrition is impossible, in cases of accumulation of uraemic toxins in the blood (uraemia) the elimination of which can not be managed by peritoneal dialysis, very high levels of fat in the blood (hyperlipidaemia). Undesirable effects: Infections: Peritonitis (very common); skin exit site and tunnel infections (very common); in very rare cases sepsis. Disorders of the hormone balance for solutions containing 1.25 mmol/l calcium: Overactivity of the parathyroid gland with potential disorders of the bone metabolism. Metabolism and nutrition disorders: Increased blood sugar and fat levels; increase in body weight due to the continuous uptake of glucose from the peritoneal dialysis solution. Cardiac and vascular disorders: Frequent pulse; decreased or increased blood pressure. Respiratory disorders: Shortness of breath due to elevation of the diaphragm, shoulder pain. Gastrointestinal disorders: Diarrhoea; constipation; hernia (very common); abdominal distension and sensation of fullness. Renal disorders: Electrolyte disturbances, e.g. decreased potassium levels (very common), increased calcium levels in combination with an increased calcium uptake, e.g. by the administration of calcium containing phosphate binders or decreased calcium levels for solutions containing 1.25 mmol/l calcium. General disorders and administration/catheter site conditions: General malaise; redness, swellings, exudations, crusts and pain at the catheter exit site; dizziness; oedema; disturbances in hydration indicated either by a rapid decrease (dehydration) or increase (overhydration) in body weight. Severe dehydration might occur when using solutions of higher glucose concentration. Peritoneal dialysis procedure related disorders: Cloudy effluent; in- and outflow disturbances of the dialysis solution. Warnings and Precautions: Do not use unless solution is clear and container undamaged. For single use only. Any unused portion of the solution is to be discarded. Do not use before mixing both solutions. The ready-to-use solution must be used within 24 hours after mixing. Do not store below 4 °C. Date: December 2006. Fresenius Medical Care Deutschland GmbH, 61346 Bad Homburg v.d.H., Germany

Composition – 1 litre of the neutral ready-to-use solution contains:

Active substances in g/l

balance1.5% Glucose1.75 mmol/l Calcium






Sodium chloride 5.640 5.640 5.640 5.640 5.640 5.640

Sodium lactate (as sodium lactate solution)

3.925 3.925 3.925 3.925 3.925 3.925

Calcium chloride dihydrate 0.2573 0.2573 0.2573 0.1838 0.1838 0.1838

Magnesium chloride hexahydrate 0.1017 0.1017 0.1017 0.1017 0.1017 0.1017

Glucose, anhydrous (as glucose monohydrate)

15 22.73 42.5 15 22.73 42.5

Active substances in mmol/l

Theoretical osmolarity (mosm/l) 358 401 511 356 399 509

balance 1.5% glucose, 1.75 mmol/l calcium, solution for peritoneal dialysisbalance 2.3% glucose, 1.75 mmol/l calcium, solution for peritoneal dialysisbalance 4.25% glucose, 1.75 mmol/l calcium, solution for peritoneal dialysisbalance 1.5% glucose, 1.25 mmol/l calcium, solution for peritoneal dialysisbalance 2.3% glucose, 1.25 mmol/l calcium, solution for peritoneal dialysisbalance 4.25% glucose, 1.25 mmol/l calcium, solution for peritoneal dialysis

These solutions are delivered in a double chamber bag. One chamber contains the alkaline lactate solution, the other chamber contains the acidic glucose-based electrolyte solution. Mixing of both solutions by opening the middle seam between the two chambers results in the neutral ready-to-use solution.

2

P3 Prolong

Protect Preserve

Preserve With balance, Fresenius Medical Care offers a biocompatible dialysis solution with ultra-low glucose degradation product (GDP) content and a neutral pH. Compared with conventional fluids, this powerful combination aims at improving survival by reducing complications in PD.1, 2

Preserve is designed to:• Preserve the peritoneal membrane function• Reduce the incidence of infection and prevalence of inflammation • Preserve residual renal function (RRF)• Improve patient survival

P3 – A new approach to Peritoneal Dialysis

P3 is a comprehensive PD programme specifically designed to improve your patients’ quality of life whilst extending their time on PD.

P3 allows you to prescribe individual therapy programmes, monitor patient conditions, and precisely adjust therapy when needed – in an efficient and optimised way.

P3 features three integrated categories: • Protect: unique and easy-to-understand PD systems• Preserve: ultra-low GDP fluids with neutral pH• Prolong: individual state-of-the-art therapies for fluid balance control and guided prescription modelling

Na+ 134 134 134 134 134 134Ca2+ 1.75 1.75 1.75 1.25 1.25 1.25Mg2+ 0.5 0.5 0.5 0.5 0.5 0.5Cl- 101.5 101.5 101.5 100.5 100.5 100.5Lactate 35 35 35 35 35 35Glucose 83.2 126.1 235.8 83.2 126.1 235.8

1 Lee HY, Park HC, Seo BJ, Do JY, Yun SR, Song HY, Kim YH, Kim YL Kim YS, Ahn C, Kim MJ, and Shin SK. Superior patient survival for continuous ambulatory peritoneal dialysis patients treated with a peritoneal dialysis fluid with neutral pH and low glucose degradation concentration (balance). Perit Dial Int 2005;25(3):248-255.

2 Lee YL, Choi HY, Park HC, Seo BJ, Do JY, Yun SR, Song HY, Kim YH, Kim YL, Kim DJ, Kim YS, Kim MJ, and Shin SK. Changing prescribing practice in CAPD patients in Korea: increased utilization of low GDP solutions improves patient outcome. Nephrol Dial Transplant 2006;21(2):2893-2899.

3 Niwa H, Takeda A, Wakai M, et al. Accelerated formation of N epsilon-(carboxymethyl) lysine, an advanced glycation end product, by glyoxal and 3-deoxyglucosone in cultured rat sensory neurons. Biochem Biophys Res Commun 1998;248:93-7.

4 Lamb EJ, Cattell WR, Dawnay AB. In vitro formation of advanced glycation end products in peritoneal dialysis fluid. Kidney Int 1995;47:1768-1774.

5 Schalkwijk CG, Posthuma N, ten Brink HJ, ter Wee PM, Teerlink T. Induction of 1,2-dicarbonyl compounds, intermediates in the formation of advanced glycation end-products, during heat-sterilization of glucose-based peritoneal dialysis fluids. Perit Dial Int 1999;19:325-333.

6 Witowski J, Wisniewska J, Korybalska K, Bender TO, Breborowicz A, Gahl GM, Frei U, Passlick-Deetjen J, Jörres A. Prolonged exposure to glucose degradation products impairs viability and function of human peritoneal mesothelial cells. J Am Soc Nephrol 2001;12(11):2434-41.

7 Schwenger V, Morath C, Salava A, Amann K, Seregin Y, Deppisch R, Ritz E, Bierhaus A, Nawroth PP, Zeier M. Damage to the peritoneal membrane by glucose degradation products is mediated by the receptor for advanced glycation end-products. J Am Soc Nephrol 2006;17(1):199-207.

8 Henderson, IS, Couper, IA & Lumsden, A: Potentially irritant glucose metabolites in unused CAPD-fluid, in Frontiers in Peritoneal Dialysis, 1985, edited by Maher JF, Winchester JF, New York, Field, Rich, pp 261–264.

9 Szeto CC, Chow KM, Lam CWK, Leung CB, Kwan BCH, Chung KY, Law MC, Li PKT. Clinical biocompatibility of a neutral peritoneal dialysis solution with minimal glucose-degradation products – A 1-year randomized control trial. Nephrol Dial Transplant 2007;22:552-559.

10 Furkert J, Zeier M, Schwenger V. Effects of peritoneal dialysis solutions low in GDPs on peritonitis and exit-site infection rates. Perit Dial Int 2008;28(6):637-40.

11 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 1997;51(1):182-6.

12 Honda K, Nitta K, Horita S, Yumura W, Nihei H, Nagai R, Ikeda K, Horiuchi S. Accumulation of advanced glycation end products in the peritoneal vasculature of continuous ambulatory peritoneal dialysis patients with low ultra-filtration. Nephrol Dial Transplant 1999;14(6):1541-9.

13 Williams JD, Topley N, Craig KJ, Mackenzie RK, Pischetsrieder M, Lage C,Passlick-Deetjen J; Euro Balance Trial Group. The Euro-Balance Trial: the effect of a new biocompatible peritoneal dialysis fluid (balance) on the peritoneal membrane. Kidney Int 2004;66(1):408-18.

14 Müller-Krebs S, Kihm LP, Zeier B, Gross ML, Deppisch R, Wieslander A, Henle T, Penndorf I, Oh J, Reiser J, Nawroth PP, Zeier M, Schwender V. Renal toxicity mediated by glucose degradation products in a rat model of advanced renal failure. Eur J Clin Invest 2008;38(5):296-305.

15 Müller-Krebs S, Kihm LP, Zeier B, Gross M-L, Haug U, Zeier M, Schwenger V. Glucose degradation products mediate cardiovascular toxicity in peritoneal dialysis. WCN 2009.

16 Zheng ZH, Anderstam B, Qureshi AR, Heimbürger O, Wang T, Södersten P, Bergström J, Lindholm B. Heat sterilization of peritoneal dialysis solutions influences ingestive behavior in non-uremic rats. Kidney Int 2002;62(4):1447-53.

17 Erixon M, Wieslander A, Lindén T, Carlsson O, Forsbäck S, Svensson E, Jönsson JA, Kjellstrand P. How to avoid glucose degradation products in peritoneal dialysis fluids. Perit Dial Int 2006;26(4):490-497.

18 Tauer A, Knerr T, Niwa T, Schaub TP, Lage C, Passlick-Deetjen J, Pischetsrieder M. In vitro formation of N(epsilon)-(carboxymethyl)lysine and imidazolones under conditions similar to continuous ambulatory pertioneal dialysis. Biochem Biophys Res Commun 2001;280(5):1408-14.

19 Zimmeck T, Tauer A, Fuenfrocken M, Pischetsrieder M. How to reduce 3-deoxyglucosone and acetaldehyde in peritoneal dialysis fluids. Perit Dial Int 2002;22(3):350-6.

20 Frischmann M, Spitzer J, Fünfrocken M, Mittelmaier S, Deckert M, Fichertb T, Pischetsrieder M. Development and validation of an HPLC method to quantify 3,4-dideoxyglucosone-3-ene in peritoneal dialysis fluids. Biomed Chromatogr 2009; 23: 843–851.

21 Lo WK, Lui SL, Chan TM, Li FK, Lam MF, Tse KC, Tang SC, Choy CB, Lai KN. Minimal and optimal peritoneal Kt/V targets: Results of an anuric peritoneal dialysis patient’s survival analysis. Kidney Int 2005;67(5):2032-8.

22 Montenegro J, Saracho R, Gallardo I, Martínez I, Munoz R and Quintanilla N. Use of pure bicarbonate-buffered peritoneal dialysis fluid reduces the incidence of CAPD peritonitis. Nephrol Dial Transplant 2007;22(6):1703-1708.

23 Mortier S, De Vriese AS, McLoughlin RM, Topley N, Schaub TP, Passlick-Deetjen J, Lameire NH. Effects of conventional and new peritoneal dialysis fludis on leukocyte recruitment in the rat peritoneal membrane. J Am Soc Nephrol 2003;14(5):1296-306.

24 Schmitt CP, von Heyl D, Rieger S, Arbeiter K, Bonzel KE, Fischbach M, Misselwitz J, Pieper AK, Schaefer F; for the Mid European Pediatric Peritoneal Dialysis Study Group (MEPPS). Reduced systemic advanced glycation end products in children receiving peritoneal dialysis with low glucose degradation product content. Nephrol Dial Transplant 2007;22(7):2038-44.

25 Kim S, Oh J, Kim S, Chung W, Ahn C, Kim SG, Oh KH. Benefits of biocompatible PD fluid for preservation of residual renal function in incident CAPD patients: a 1-year study. Nephrol Dial Transplant 2009;24(9):2899-908.

3

GDPs and AGEs exhibit adverse local and systemic effects

GDPs are considered to play a major role in the bioincompatibility of peritoneal dialysis fluids. Glucose degradation, forming GDPs, takes place during sterilisation and storage of PD fluids. In addition to their direct toxicity, GDPs promote the formation of advanced glycation end products

(AGEs), in particular 3-deoxyglucosone (3-DG).3, 4, 5 Both GDPs and AGEs have negative local and systemic effects: • by affecting cell viability and function6

• by inducing inflammation, fibrosis and neo- angiogenesis7

Preserving systemic homeostasis

Systemic effects of GDPs and AGEs• Reduction of residual renal function13, 14

• Cardiovascular toxicity15

• Increased inflammation9

• Reduced appetite16

Local effects of GDPs and AGEs• Inflow associated pain8

• Increased inflammation/infection9, 10 • Damage to the peritoneal membrane11

• Loss of ultrafiltration12

Peritoneal cavity Peritoneal membrane

GDPs

Protein

AGEs

+

Mesothelial cell Blood vessel

6

In addition to local toxic effects, GDPs and AGEs cause systemic toxicity which has been shown to be associated with a decline in RRF13, 14 and cardio-vascular damage.15

balance • reduces systemic AGE formation13, 24 • decreases systemic inflammation9

• preserves residual renal function13, 25

Preserving residual renal function contributes to survival and the quality of life of PD patients.1, 2 RRF eliminates middle molecules, increases hemoglobin, improves acid base balance and nutritional status, as well as fluid balance.

The challenge in PD is to improve technique and patient survival. Thanks to the beneficial effects of balance, we have the potential to contribute to this goal.

balance preserves the RRF

GF

R L

/min

/1.7

3 m

2

75

50

25

0

balance


1 7 13Time (month)

Positive effect of balance on the RRF in patients with a glomerular filtration rate (GFR) of ≥ 2 mL/min/1.73 m2. 25

Chart adapted from Kim et al.25

Lower systemic inflammation with balance

Positive effect of balance on the C-reactive protein (CRP) serum levels.9

Ser

um C

RP

(mg

/l)

12

8

4

0

52 weeks

Overall ANOVA (p = 0.025)

balanceConventional PD fluid

p = 0.004

Smart technology dramatically reduces GDPs

balance contains ultra-low GDP concentrations by utilising a double-chamber bag system. The formation of GDPs is drastically reduced by separating the glucose from the buffer which allows sterilization and storage of glucose at a low pH. Immediately before infusion both chambers are mixed, which results in a unique biocompatible solution with neutral pH and ultra-low GDP content.17, 18 This greatly reduces the unfavourable effects associated with GDPs and AGEs.

balance• Ultra-low GDP fluid with neutral pH• Lactate-buffered solution

4 5

Preserving the peritoneal membrane function

Preservation of the peritoneal membrane function is central to the effective treatment of PD patients.21

balance • reduces the risk of damage to the peritoneal membrane13

• improves mesothelial cell mass/function as indicated by increased CA-12513

• reduces peritoneal inflammation and damage as indicated by decreased hyaluronan13

• has shown excellent reduction in infection rates2, 23

Conventional PD fluids can alter the peritoneal membrane over

time and might lead to functional problems. This process shall be

delayed with more biocompatible PD fluids.

Profile of the parietal peritoneal membrane at (left) therapy

initiation and (right) > 5 years therapy (The Peritoneal Biopsy

Registry®)

200 µm 200 µm

balance is the only PD fluid with ultra-low GDPs17, 19, 20

3-D

G* (µ

mo

l/l)

250

200

150

100

50

0balance Competitor

PD fluid 1

PD Fluids* 3-deoxyglucosone; 2.3% glucose, 2.27% glucoseChart based on Erixon et at.17

Competitor PD fluid 2

biocompatible conventional

Improved mesothelial cell mass/function

CA125 values were significantly higher in patients on balance, suggesting better preserved mesothelial cell mass/function with balance.13


Reduced peritoneal inflammation

Effl

uent

hya

luro

nan

(ng

/ml)

1500

1000

500

0Month 3 Month 6

p < 0.01

Hyaluronan was significantly decreased in patients treated with balance indicating reduced peritoneal inflammation.13

Effl

uent

CA

125

(U/m

l)

100

80

60

40

20

0Month 3 Month 6

p < 0.001

mes

othe

lial c

ell


Gambrosol Trio

3

GDPs and AGEs exhibit adverse local and systemic effects

GDPs are considered to play a major role in the bioincompatibility of peritoneal dialysis fluids. Glucose degradation, forming GDPs, takes place during sterilisation and storage of PD fluids. In addition to their direct toxicity, GDPs promote the formation of advanced glycation end products

(AGEs), in particular 3-deoxyglucosone (3-DG).3, 4, 5 Both GDPs and AGEs have negative local and systemic effects: • by affecting cell viability and function6

• by inducing inflammation, fibrosis and neo- angiogenesis7

Preserving systemic homeostasis

Systemic effects of GDPs and AGEs• Reduction of residual renal function13, 14

• Cardiovascular toxicity15

• Increased inflammation9

• Reduced appetite16

Local effects of GDPs and AGEs• Inflow associated pain8

• Increased inflammation/infection9, 10 • Damage to the peritoneal membrane11

• Loss of ultrafiltration12

Peritoneal cavity Peritoneal membrane

GDPs

Protein

AGEs

+

Mesothelial cell Blood vessel

6

In addition to local toxic effects, GDPs and AGEs cause systemic toxicity which has been shown to be associated with a decline in RRF13, 14 and cardio-vascular damage.15

balance • reduces systemic AGE formation13, 24 • decreases systemic inflammation9

• preserves residual renal function13, 25

Preserving residual renal function contributes to survival and the quality of life of PD patients.1, 2 RRF eliminates middle molecules, increases hemoglobin, improves acid base balance and nutritional status, as well as fluid balance.

The challenge in PD is to improve technique and patient survival. Thanks to the beneficial effects of balance, we have the potential to contribute to this goal.

balance preserves the RRF

GF

R L

/min

/1.7

3 m

2

75

50

25

0

balance


1 7 13Time (month)

Positive effect of balance on the RRF in patients with a glomerular filtration rate (GFR) of ≥ 2 mL/min/1.73 m2. 25

Chart adapted from Kim et al.25

Lower systemic inflammation with balance

Positive effect of balance on the C-reactive protein (CRP) serum levels.9

Ser

um C

RP

(mg

/l)

12

8

4

0

52 weeks

Overall ANOVA (p = 0.025)


p = 0.004

Preserve - fmc-my.com Preserve.pdf · Protect Preserve Preserve ... Yun SR, Song HY, Kim YH, Kim YL...

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