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The Importance of Residual Renal Function

The Importance of Residual Renal Function. Dr Paul Tam June 11, 2010. Loss of RRF. Resting hypermetabolism. Malnutrition. Inflammation. Cardiovascular Disease. Increased Mortality and Cardiovascular Death. RRF, an important predictor of survival in dialysis patients.

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The Importance of Residual Renal Function

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  1. The Importance of Residual Renal Function Dr Paul Tam June 11, 2010

  2. Loss of RRF Resting hypermetabolism Malnutrition Inflammation Cardiovascular Disease Increased Mortality and Cardiovascular Death RRF, an important predictor of survivalin dialysis patients

  3. Importance of RRF • Average GFR at dialysis initiation : 6.6 to 8.0 ml/min (USRDS 99 Annual Data Report • Each 1ml/min of residual renal GFR translate into CCr of 10 L/Week and Kt/v urea of 0.25 to 0.3/Week (70kg male) • Improved clinical outcomes with better small solute clearences

  4. Importance of RRF • Reanalysis of CANUSA study: For each 5L/wk/1.7.73 m increment in GFR; there was 12% decrease in RR of death. (RR0.88; Cl 0.83-0.94) • No association with peritoneal creatinine clearance (RR 1.0, Cl 0.9-1.10) • Peritoneal and renal clearance not equivalent • 24 h urine volume is even more important than GFR (250ml/day 36% in RR of deaths) Bargman et al. J am Soc Nephrol 12:2158-2158-2162, 2001

  5. ADEquacy of Peritoneal Dialysis in MEXico (ADEMEX) study • Residual renal and peritoneal dialysis clearance are not equivalent and thus not simply additive. • Increasing peritoneal solute clearence showed no beneficial effect on survival in PD patients. • Residual renal function was predictive of outcome. Paniagua et al. Am Soc Nephrol, 2002

  6. Clearance effect on outcomes in PD

  7. Patient survivalTermorshuizen et al. J Am Soc Nephrol 2004 The residual renal function (rKt/Vurea) and dose of dialysis (sp-dKt/Vurea) werLe included as time-dependent variables. RR, relative risk; CI, confidence interval.

  8. The effect of single-pool Kt/Vurea (sp-dKt/Vurea) on mortality by presence of residual renal function (rKt/Vurea = 0 ["anurics'" versus rKt/Vurea >0) Termorshuizen, F. et al. J Am Soc Nephrol 2004

  9. Potential mechanisms of benefit of RRF in dialysis

  10. Effects of additional of dialysis clearences to a glomerular filtration rate of 5ml/min Krediet,KI 2006

  11. Peritoneal, renal, and total clearances of urea nitrogen (UN), creatinine (Cr), phosphate (P), 2-microglobulin ( B2M), and p-cresol. Bammens et al. Kidney International (2003) 64, 2238–2243

  12.  Residual renal function Resting energy expenditure  Removal of middle moleculer uremic toxins Toxins, such as p-cresol  Sodium and fluid removal  Clearence of urea and creatinine  P removal  EPO production  Inflammation  Cardiac hyperthyrophy  Atherosclerosis and arteriosclerosis  malnutrition  Vascular and valvular calcification  Overall and cardiovascular mortality  Quality of life Wang and Lai KI 2006

  13. Fig.   ECW in patients with rGFR <2 and >2 ml/min ECW:extracellular volume determined by bromide dilution, corrected for height. the 25th–75th percentile range (line across box=median). Capped bars: minimum and maximal values (with exception of outliers). Konings, C. J. A. M. et al. Nephrol. Dial. Transplant. 2003 18:797-803;

  14. Left Ventricular Mass in Chronic Kidney Disease and ESRD “A new paradigm of therapy for CKD and ESRD that places prevention and reversal of LVH and cardiac fibrosis as a high priority is needed.” Richard J. Glassock et al, CJASN 4: s79-91s

  15. Mean arterial pressure and RRF over time from initiation of peritoneal dialysis Menon, M. K. et al. Nephrol. Dial. Transplant. 2001 16:2207-2213;

  16. Nutritional parameters in patients with and RRF Suda, T. et al. Nephrol. Dial. Transplant. 2000 15:396-401

  17. Is the rate of decline of RRF between HD and PD different?

  18. CCr ml/min Residual renal function is preserved longer in peritoneal dialysis (PD) Rottembourg J. Perit Dial Bull 1986

  19. PD PD HD HD B A Figure:Unadjusted (A) and adjusted (B) residual glomerular filtration rate (rGFR) values SE at the start of dialysis treatment, and at 3, 6 and 12 months after the start of dialysis treatment. Jansen et al KI 2002

  20. Decline of residual renal function is faster on HD than on PD

  21. Does PD have a protective effect on RRF? • Less abrupt fluctuations in volume and osmotic load in PD • Intradialytic hypotension and volume fluctations in HD • Patients on PD are in slightly volume-expanded state • Bioincompatible membranes in HD • PD might delay the progression of advanced renal failure

  22. Do biocompatible PD solutions or biocompatible dialyser membranes have any advantage in relation to RRF?

  23. The Euro-Balance Trial Williamset al KI 2004

  24. Dialysis adequacy, residual renal function and nutritional indices Szeto et al. NDT 2007

  25. Effect of biocompatible (B) vs standard (S) PD solutions on RRF (mean of urea and nCrCl) Fan et al KI 2008

  26. Effect of biocompatible (B) vs standard (S) PD solutions on 24-h Uvol (mean/s.e.m.). Fan et al KI 2008

  27. New multicompartmental PD fluids

  28. Preserving residual renal function in peritoneal dialysis: volume or biocompatibility? Davies, Simon NDT 23, June 2009 24, 2620-2622

  29. Majority of studies indicate RRF is relatively well preserved with PD in comparison to HD Davies, Simon NDT 23, June 2009 24, 2620-2622

  30. Studies Reviewed Davies, Simon NDT 23, June 2009 24, 2620-2622

  31. Hypothesis???? • Relative stability of volume in PD, where as HD fluctuations in volume are common • Biocompatibility of the dialysis fluids “The new biocompatible solutions may help preserve RRF, but the mechanisism is not certain and an inadvert effect on fluid status seems likely – at least in some of the studies.” Davies, Simon NDT 23, June 2009 24, 2620-2622

  32. Low-GDP Fluid (Gambrosol Trio) Attenuates Decline of Residual Renal Function (RRF) in PD Patients: A Prospective Randomized Study(DIUREST Study)NDT March 2010

  33. Background Clinical study in PD patients regarding content of GDP on PD fluid and its influence on the decline of RRF RRF impacts outcome & survival of PD patients Morbidity, poor nutrition & fluid overload associated with decline of RRF Glucose degradation products (GDPs): Affect cell system and tissues Act as precursors of advanced glycosylation endproducts (AGEs) locally and systemically

  34. Methods Study design A Multicentre, prospective, randomized, controlled, open, parallel, 18 month study 80 patients randomized through stratification for the presence of diabetes • Inclusion • Age: 18-80 with ESRD • GFR ≥ 3mL/min or CrCl ≥ 6mL/min • HBV, HCV, HIV negative • Exclusion • Pregnancy or lactating subjects • Several peritonitis episodes • Cancer

  35. Study centers in: Germany(15) France (7) Austria (1) Solutions Treatment solution Gambrosol trio Control (Standard) solution: Gambrosol (50% of patients) Stay-safe (31% of patients) Dianeal (19% of patients)

  36. Follow-up 4 - 6 weeks Serum U & Cr, CRP, T. Protein, albumin, lytes, phosphate 24 Hr. Urine: CrCl & UrCl BP & Wt UF At 1, 6, 12, 18 months CA125 Personal Dialysis Capacity (PDC) Medications: ACE & ARBs Diuretics Phosphate binders

  37. Results Subjects 44 (Treatment: 1 was intend-to-treat) Recruited: 80 36 (Standard) Median exposure time: Treatment solution 17.8 m Standard solution 16.3 m Dropout: 11 before first RRF measurement N=69 with 2.4% /month dropout rate

  38. Clinical Significance RRF: Treatment group higher by 2.3 ml/min/1.73 m2 24 H Urine volume: less decline in Treatment group by three-fold Phosphate control: better in Treatment group by five-fold CA125: higher levels in Treatment group UF volumes not conclusive due to unreliability of data D/P & PDC parameters no significant changes, possibly due to patient dropout & missing data

  39. Limitations Inconsistency in control group (?) Patients’ selection: incident & prevalent patients Large dropout rate Unreliability of data on UF & D/P properties Consistency issue with testing of CA125 Effects of different antihypertensive use with their potential effect on RRF

  40. Strategies for preservation of RRF • Avoidance of hypovolemia • Avoidance of potentially nephrotoxic drugs • The use of high dose of loop diuretics • The use of an ACE inhibitor or A-II reseptor antogonist • Starting dialysis with PD

  41. In HD patients • Prevention of intradialytic hypotensive episodes • Developing a highly biocompatible HD system includinga synthetic membrane and ultrapure dialysis fluid.

  42. Biocompability of dialyser membranes

  43. In PD patients • Prevention of hypotension and fluid volumedepletion • Optimization of blood pressure control • Usage of biocompatible and smoother ultrafiltrationprofile • Preservation of peritoneal permeabilitycapacity • Prevention of peritoneal dialysis-related peritonitis

  44. ConclusionThe potential benefits of RRF • Better clearence of middle and larger molecular weights toxins, • Better volume and blood pressure control • Improved appetite and nutritional status • Relative preservation of renal endocrine functions • Improved phosphate control • Improved quality of life

  45. Conclusion • Beneficial effect of RRF has been reported both in PD or HD patients. • One potential strategy to preserve RRF may be to preferentially use PD over HD in incident patients with RRF.

  46. Questions? Comments? Thank You

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