1. Nuevas Soluciones en DP, Sirven? Prueba en diabéticos con transporte peritoneal alto y promedio alto Dr. José Ramón Paniagua Sierra Unidad de Investigación Médica en Enfermedades Nefrológicas. UMAE HE CMN S XXI, México, D. F. Dr. José Ramón Paniagua Sierra Unidad de Investigación Médica en Enfermedades Nefrológicas. UMAE HE CMN S XXI, México, D. F.

2. Background  Sodium intake and extracellular fluid volume expansion have been associated with hypertension and cardiovascular mortality in the general population  Extracellular fluid volume expansion is the most frequent cause of hypertension in ESRD patients with or without dialysis treatment. It has been related with other predictors of death like left ventricular hypertrophy  Extracellular fluid volume expansion has also been related with lost of RRF and low grade chronic inflammation  Sodium intake and extracellular fluid volume expansion have been associated with hypertension and cardiovascular mortality in the general population  Extracellular fluid volume expansion is the most frequent cause of hypertension in ESRD patients with or without dialysis treatment. It has been related with other predictors of death like left ventricular hypertrophy  Extracellular fluid volume expansion has also been related with lost of RRF and low grade chronic inflammation

3. Background  Several clinical conditions and serum markers are now known as predictors of clinical outcomes in ESRD patients. Among them: Diabetes Cardiovascular morbidity (LVH, HT, proBNP, TNt) Malnutrition (SA, TF, LBM, TBW, MAC) Inflammation (CRP, TNF , IL-6) Fluid and sodium removal  The variety of predictors suggest a complex network of interactions between them. ECFv expansion may have a significant role  Several clinical conditions and serum markers are now known as predictors of clinical outcomes in ESRD patients. Among them: Diabetes Cardiovascular morbidity (LVH, HT, proBNP, TNt) Malnutrition (SA, TF, LBM, TBW, MAC) Inflammation (CRP, TNF , IL-6) Fluid and sodium removal  The variety of predictors suggest a complex network of interactions between them. ECFv expansion may have a significant role

4. ADEMEX Mortality

5. IL 6 and mortality

6. C-reactive protein and mortality

7. Fluid removal and mortality

8. pBNP and mortality

9. Relationship of inflammation, ECFv and DM MALNUTRITION OR WASTING MALNUTRITION OR WASTING INFLAMMATION CV DISEASE CV DEATH

10. Relationship of inflammation,ECFv and DM MALNUTRITION OR WASTING MALNUTRITION OR WASTING INFLAMMATION CV DISEASE CV DEATH ECFv EXPANSION ECFv EXPANSION PERITONEAL PERMEABILITY PERITONEAL PERMEABILITY  PRESSURE  VOLUME  PRESSURE  VOLUME

11. Relationship of inflammation, ECFv and DM MALNUTRITION OR WASTING MALNUTRITION OR WASTING INFLAMMATION CV DISEASE CV DEATH ECFv EXPANSION ECFv EXPANSION PERITONEAL PERMEABILITY PERITONEAL PERMEABILITY  PRESSURE  VOLUME  PRESSURE  VOLUME D M CHO-PTG D M CHO-PTG      ?        

12. Background  The success in the control of ECFv of PD patients depends on: Sodium and fluid intake Residual renal function Peritoneal transport type (PET) Type and concentration of the osmotic agent in the dialysis solution  The success in the control of ECFv of PD patients depends on: Sodium and fluid intake Residual renal function Peritoneal transport type (PET) Type and concentration of the osmotic agent in the dialysis solution

13. Background  Glucose is the most commonly used osmotic agent. Disadvantages: Damage of mesothelial cells by glucose degradation products and advanced glycation products Peritoneal glucose absorption. Then:  Loss of osmotic gradient = deficient UF  Obesity, low protein intake, impairment in metabolic control  Diabetes increases glucose disadvantages  Glucose is the most commonly used osmotic agent. Disadvantages: Damage of mesothelial cells by glucose degradation products and advanced glycation products Peritoneal glucose absorption. Then:  Loss of osmotic gradient = deficient UF  Obesity, low protein intake, impairment in metabolic control  Diabetes increases glucose disadvantages

14. Icodextrin  It has been successfully used as osmotic agent, particularly in high transporters  It does not have the glucose disadvantages  It has been successfully used as osmotic agent, particularly in high transporters  It does not have the glucose disadvantages Chain α (1→4) Chain α (1→6)

15. Background  In spite of the potential benefits of icodextrin in increasing ultrafiltration without metabolic disadvantages in high-transport diabetic PD patients, RCT are not available  Information is important for populations with high rates of diabetics in their PD programs. This is the case of Mexico and other countries.  In spite of the potential benefits of icodextrin in increasing ultrafiltration without metabolic disadvantages in high-transport diabetic PD patients, RCT are not available  Information is important for populations with high rates of diabetics in their PD programs. This is the case of Mexico and other countries.

16. Objective  Primary outcomes: Improvement in peritoneal UF Reduction of ECFv Control of BP, edema and CV function Metabolic control  Primary outcomes: Improvement in peritoneal UF Reduction of ECFv Control of BP, edema and CV function Metabolic control  Secondary outcomes: Nutrition improvement Control of inflammation Quality of life Mortality  Secondary outcomes: Nutrition improvement Control of inflammation Quality of life Mortality To test the clinical usefulness of icodextrin based solution in high transport diabetic patients in PD

17. Study design Target of treatment  To reach control of blood pressure and edema through the increment in peritoneal ultrafiltration Treatments. 3x2L, 1.5% glucose exchanges plus:  Control group: Glucose-based solutions, at least 1 bag with 2.5% glucose in the longest dwell  Icodextrin group: Icodextrin-based solution (7.5%) in the longest dwell Replacement of 1.5% for 2.5 or 4.25% glucose was allowed to reach the treatment goal  To reach control of blood pressure and edema through the increment in peritoneal ultrafiltration Treatments. 3x2L, 1.5% glucose exchanges plus:  Control group: Glucose-based solutions, at least 1 bag with 2.5% glucose in the longest dwell  Icodextrin group: Icodextrin-based solution (7.5%) in the longest dwell Replacement of 1.5% for 2.5 or 4.25% glucose was allowed to reach the treatment goal

18. Study design  Randomized clinical trial Open label Multicentric (HGZ 8; HGZ 25; HGZ 27; HGZ 47. IMSS, México, D. F.) Central randomization Central laboratory (UIMEN) Follow-up: 6 months; 12 months  Randomized clinical trial Open label Multicentric (HGZ 8; HGZ 25; HGZ 27; HGZ 47. IMSS, México, D. F.) Central randomization Central laboratory (UIMEN) Follow-up: 6 months; 12 months

19.  Inclusion criteria Diabetics Adults High and high average transport Without selection by gender or time on dialysis  No inclusion criteria Seropositivity HB, HIV CA, immunosuppression  Inclusion criteria Diabetics Adults High and high average transport Without selection by gender or time on dialysis  No inclusion criteria Seropositivity HB, HIV CA, immunosuppression  Exclusion criteria Patient decision Medical decision Transplant Change of address  Exclusion criteria Patient decision Medical decision Transplant Change of address Material and methods Patients

20. Results Without differences between groups at baseline in:  Age  Gender  Blood pressure  Body composition  Dialysis adequacy  Biochemical parameters  Comorbidity Without differences between groups at baseline in:  Age  Gender  Blood pressure  Body composition  Dialysis adequacy  Biochemical parameters  Comorbidity

21. Results  Prescription In the control group two thirds of the patients needed more than one bag of 2.5% glucose or at least one bag of 4.25% glucose. In the icodextrin group only 9% needed a bag with more than 1.5% of glucose  Prescription In the control group two thirds of the patients needed more than one bag of 2.5% glucose or at least one bag of 4.25% glucose. In the icodextrin group only 9% needed a bag with more than 1.5% of glucose

22. Results Actual prescription

23. Results Metabolic control

24. Results

26. Mean±EEM *p<0.05; ** p<0.03; *** p<0.01 vs Control ‡p<0.05; ‡ ‡ p<0.03; ‡ ‡ ‡ p<0.01 vs Basal Mean±EEM *p<0.05; ** p<0.03; *** p<0.01 vs Control ‡p<0.05; ‡ ‡ p<0.03; ‡ ‡ ‡ p<0.01 vs Basal Results

32. Body fluids and cardiovascular parameters

33. Results Ultrafiltration

34. Results

35. Results BP (in office)

36. Results BP (ambulatory) **  ** * *** ** ** *= p<0.05 vs basal; **= p<0.01 vs basal;  = p<0.05 vs glucose group;   = p<0.01 vs glucose group

37. Results EKG basal

38. Results EKG changes

39. Results Icodextrin metabolites

41. Results Mortality ( ) = number of patients. *= Death related to dropout cause. [ ] Dialysis modality at the time of death Death was considered related to dropout case if occurred in the 30 days after dropout and the final diagnosis was related to the technique failure

42. Results Mortality

44. Annual Cost of Patient on Dialysis $- $50 $100 $150 $200 $250 $300 APDCAPD Icodextrin CAPDDPHD INSTHD SUB x1000 ConsumablesPharmacologic tLaboratoryHospitalizationPeritonitisCatheter dysfunction DisabilityEmergencyPersonalInfrastructureTransport Results

45. Relationship of inflammation, ECFv and DM MALNUTRITION OR WASTING MALNUTRITION OR WASTING INFLAMMATION CV DISEASE CV DEATH ECFv EXPANSION ECFv EXPANSION PERITONEAL PERMEABILITY PERITONEAL PERMEABILITY  PRESSURE  VOLUME  PRESSURE  VOLUME D M CHO-PTG D M CHO-PTG X   ? xx xx xx xx X  ICODEXTRIN

46. Conclusion  Patients in the Icodextrin group had better metabolic control and nutrition  Icodextrin-based solution was superior to glucose- based solution in fluid and sodium removal.  Patients in the Icodextrin group had better control of blood pressure and reduction in left ventricular mass  Patients in the Icodextrin group had better metabolic control and nutrition  Icodextrin-based solution was superior to glucose- based solution in fluid and sodium removal.  Patients in the Icodextrin group had better control of blood pressure and reduction in left ventricular mass