EMODIALISI NOTTURNA. dr.ssa Patrizia Ondei. U.O. Nefrologia e Dialisi. A.O. Papa Giovanni XXIII Bergamo

Transcription

1 EMODIALISI NOTTURNA dr.ssa Patrizia Ondei U.O. Nefrologia e Dialisi A.O. Papa Giovanni XXIII Bergamo XXII Corso Nazionale di Aggiornamento ANTE 31 Marzo- 2 Aprile 2014 Riccione

2 1943 first recovery of an acute renal failure patient treated with a rotating drum hemodialysis system designed by WILLEM KOLFF. This was the beginning of what was to become an important clinical reality: artificial renal substitution therapy.

3 The paradigm of hemodialysis has so evolved from a life-saving treatment for a minority of patients with acute kidney injury to a life sustaining therapy for many thousand of patients with chronic kidney disease stage 5 worldwide

4 The major developments in the next decades related to improvements in membrane biocompatibility and dialyzer design, volumetric control, sophisticated monitoring systems that control, sophisticated monitoring systems that provide online clearances dialysis, high flux membrane and convective modalities such as hemofiltration and hemodiafiltration

5 Adjusted mortality rates in ESRD and general populations, age 65 and older (per 1000 patient years at risk) dialysis 250 transplant cancer 200 diabetes CHF 150 CVA/TIA 100 AMI 50 0 data from 2012 USRDS annual report

6

7 Adjusted survival in incident dialysis patients and patients receiving a first transplant (between 2001 and 2005) from day 91, by modality, adjusted for age, gender, and primary diagnosis

8 Cardiovascular disease mortality in the general population and dialysis patients Parfrey et al. J Am Soc Nephrol (1999)

9 HEMO study 1846 patients mean follow-up 2,84 years randomization to either standard- or high-dose goal and either low or high-flux dialyzer Eknoyan et al. N Engl J Med (2002)

10 Hemodialysis Study Group Conclusions. In summary, altough the effect of the dose and level of membrane flux may vary among selected subgroups of patients, the primary results of our study indicate that, with a schedule of thrice-weekly dialysis, neither an increased dose of dialysis nor use of a high-flux membrane substantially improves survival, reduces the rate of hospitalization, or mantains serum albumin levels as compared with a standard dose and use of low-flux membranes. Eknoyan et al. N Engl J Med (2002)

11 The "unphysiology" of dialysis: a major cause of dialysis side effects? Kjellstrand CM et al. Kidney Int 1975 We hold this truth to be self-evident in dialysis: normal chemistries and physiology are better than abnormal a lot better In dialysis, it is more important that body chemistries are normal ( physiologic ) than that an arbitrary Kt/V is achieved. The best way, we contemplated, to get rid of "un-physiology" is to dialyze often i.e., dialyze daily. There is no possibility of keeping body chemistries within normal limits with three dialyses per week.

12 Foley RN et al. N Engl J Med (2011)

13 data from the HEMO study cubic spline interpolation suggested that the risk of mortality began to increase at ultrafiltration rates over 10 ml/h/kg Kidney Int (2011) vol. 79

14 national cohort of patients from a dialysis organization 2382 pairs matched on age, gender, access, post-dialysis weight Flythe et al. Kidney Int (2012)

15 cross-sectional study 46 patients on either conventional HD; HD 5-6 times/week in a center and at home or home nocturnal HD Jefferies et al. CJASN (2011) vol. 6

16 (2012) vol. 25 (1)...The Hippocratic Oath tells us to abstain from doing harm ; one must be concerned that standard HD, at least in some patients, violates the primum non nocere tenet of medicine. This literature and other recent studies seem to be building a case for more careful consideration of alternatives to conventional three times weekly in-center HD and movement away from cookie cutter HD...

17 (2011) vol. 24 (6)

18 Improvement in hypertension control mmhg mmhg systolic blood pressure diastolic blood pressure randomized controlled trial: 52 patients, 6 months follow-up antihypertensive medications discontinued/reduced in 16/26 NHD patients vs. 3/25 CHD patients (p<0,001) Culleton et al. JAMA (2007) vol. 298 (11)

19 Improvement in hypertension control 24h MAP (mmhg) CHD NHD 1m NHD 2m prospective observational study: 18 patients converted from CHD to NHD for 2 months significant reduction in antihypertensive medications: 2,5->0,2 meds/patient, p<0,001 Chan T. et al. Hypertension (2003) vol. 42

20 Regression of LVH mean LVMI g/m 2 52 patients randomized to NHD or CHD for 6 months LV mass assessed by cardiac MRI in 35 patients Culleton et al. JAMA (2007) vol. 298 (11)

21 Regression of LVH observational cohort study: 28 patients converted from CHD to NHD significant reduction in BP and LVMI LVMI g/m 2 baseline 147±42 year 1 130±33 year 2 106±32 year 3 102±19 LVMI correlated with systolic BP Chan et al. Kidney Int (2002) vol. 61 (6)

22 Reduction of sleep apnea conversion from CHD to NHD in 14 patients (7 with sleep apnea) reduction in the frequency of apnea and hypopnea, especially in the 7 patients with sleep apnea increase in pharyngeal cross-sectional area may play a role Hanly et al. NEJM (2001) vol. 344 Beecroft et al. NDT (2008) vol. 23

23 Enhanced ESA responsiveness NHD CHD p Hb (g/dl) 12,4±4 12±4 0,30 EPO (U/kg/w) 90.5± ± ,04 IL-6 (pg/ml) 3.9 ± ±0.8 0,04 hscrp (mg/l) 4.6 ± ± cross-sectional study on 14 NHD patients vs. 14 CHD patients matching for age and comorbidities and control for Hb concentrations and iron status Yuen et al. ASAIO Journal (2005) vol. 51

24 Improved phosphate control 51 patients randomized to CHD or NHD reduction in phosphate levels with fewer binders in HD variable effects on calcium and PTH Walsh et al. Hemodialysis International (2010) vol. 14

25 American Journal of Kidney Diseases (2003) vol. 41

26 A 42-year-old man with ESRD was referred for conversion to NHD therapy from CHD because of refractory intermittent claudication secondary to peripheral arterial disease. After conversion to NHD therapy (7.5 h/session five times weekly), the patient became symptom free and had significant clinical improvements in hemodynamics, measured by clinic blood pressure and two-dimensional echocardiography; biochemical profile, and a sustained improvement in arterial Doppler flow measured by duplex Doppler ultrasound. American Journal of Kidney Diseases (2003) vol. 41

27 Nutritional benefits 15 patients converted from CHD to NHD minimum follow-up 8 months increase in protein intake, no dietary restrictions no change in BMI and upper arm muscle circumference Ipema et al. Ren Nutr (2012)

28 Improved pregnancy outcomes case series of 6 successful pregnancies in women on NHD putative improved fertility with NHD less severe pregnancy and fetal complications than those reported in literature on CHD mean gestational age 36.2±3 weeks mean birth weight ±657 g Barua et al. CJASN (2008) vol. 3

29 Better quality of life improvement in exercise capacity Chan et al. NDT (2007) improved cognition 22% reduction in cognitive symptoms 32% improvement in attention and working memory Jassal et al Kidney Int (2006) significant improvements in selected kidney-specific domains of quality of life in NHD, without difference in overall quality of life (EuroQol 5-D index) Culleton et al. JAMA (2007)

30 Improved survival Survival of NHD patients is comparable to recipients of deceased donor kidney graft Pauly et al. NDT (2009) vol. 24 (9)

31

32 FHN Nocturnal Trial 87 patients randomized to either NHD or CHD, 12 month follow-up no significant difference in either of coprimary outcomes (death or LVM measured by MRI) better control of hyperphosphatemia and hypertension in NHD no statistically significant differences for the other main secondary outcomes ( physical health composite score, albumin, ESA dose, non-access hospitalization) trend toward an increased rate of access complications in the NHD arm Rocco et al. Kidney Int 2011

33 FHN Nocturnal Trial: major limitations limited sample size lower adherence to the dialysis prescription in NHD arm mean number of treatments 2,91±0,21 in CHD vs. 5,06±0,8 in NHD

34

35 The Tassin paradigm 1380 patients treated from 1968 to x8h/week mean delivered spkt/v >2 per session low salt diet (average 5g/day) systematic antihypertensive treatment withdrawal in conjunction with lowering of extracellular volume to achieve dry weight Charra B. Nefrologia (2005)

36 98% of patients off antihypertensive drugs average observed mortality in Tassin consistently about 45% of the expected value for US patients similar in age, race and cause of renal failure, in spite of worsening of case mix along the years Charra B. Nefrologia (2005)

37 Bergamo INHD program started in January nurse : 3 patients 1 physician till (afterwards on call) 1 reverse osmosis technician on call frequency (times/week) INHD 3 3 CHD duration (h) 8 3,5-4 QB ml/min QD ml/min dialyzer surface (m 2 ) 1,2-1,4 1,3-1,9

38 Patient population Bergamo INHD program 7 patients participation on a voluntary basis motivation to comply with the treatment schedule was required Cravedi et al. Int J Artif Organs (2009) vol. 32 (1)

39 Improved hypertension control Bergamo INHD program systolic blood pressure reduction in the mean number of antihypertensive drugs: 1,17±1,19 0,47±0,089 drugs/patient diastolic blood pressure complete withdrawal of all blood pressure lowering medications in 4 patients Cravedi et al. Int J Artif Organs (2009) vol. 32 (1)

40 Increase in body weight Bergamo INHD program pre-hd significant increase in body weight after conversion from CHD to INHD no significant change in intradialytic weight reduction post-hd Cravedi et al. Int J Artif Organs (2009) vol. 32 (1)

41 Enhanced phosphate control Bergamo INHD program Cravedi et al. Int J Artif Organs (2009) vol. 32 (1)

42 Good treatment tolerance Bergamo INHD program after 1 year of INHD, all patients declared that their mood was either good (N=1) or very good (N=6) only 2 patients reported difficulties in falling asleep during the INHD sessions, however no sleeping medications were needed Cravedi et al. Int J Artif Organs (2009) vol. 32 (1)

43

44

45

46 ...The present thrice-weekly program was easy to establish and did not significantly affect our unit s activity. Indeed, it was started with preexisting dialysis facilities. New dialysis machines, clinic space, the development of home monitoring systems, or extensive patient training were not required. However, extra payment for nurses and technicians was required

47 prospective observational study, 2 years of follow-up 746 patients starting INHD, matched 1:3 with CHD patients on the basis of propensity score: age, gender, race, diabetes, dialysis vintage, BMI, vascular access, albumin, hemoglobin, phosphorus, calcium, white blood cell count geographic area incident patient status (vintage 90 days vs. >90 days) J Am Soc Nephrol (2012) vol. 23 (4)

48 Patient survival 1-year mortality rate: 9% for INHD vs. 15% for CHD pts 2-year mortality rate: 19% in INHD vs. 27% in CHD pts Lacson et al. J Am Soc Nephrol (2012) vol. 23 (4)

49 Secondary outcomes sustained significant decline in phosphorus levels from 5.73 to 5.02 mg/dl in INHD, p<0,001 balanced increase in both interdialytic weight gain and intradialytic weight loss for INHD patients that was not evident in CHD patients better increase in albumin and hemoglobin in NHD patients, not reaching statistical significance Lacson et al. J Am Soc Nephrol (2012) vol. 23 (4)

50 prospective observational study on 247 INHD patients from 10 HD centers operated by Fresenius in Turkey 12 months follow-up 1:1 matching with CHD patients on age, sex, diabetes and dialysis vintage NHD n=247 CHD n=247 age (years) 45,2±13,9 45,8±12,9 female (%) 31,9 31,9 dialysis vintage (months) 60,6±44,9 59,5±44,4 AV fistula (%) 90,6 91,9 BMI (kg/cm 2 ) 23,1±4,6 23,6±4,8 CV disease Hx (%) 14,3 13,9 Nephrol Dial Transplant (2011) vol. 26 (4)

51 Survival and adverse events one-year survival rate 98,4% in INHD 93,9% in CHD lower hospitalization rate in the INHD group 5.43 vs days/ 100 patient-months, p=0.002 marked decrease in intradialytic hypotensions in INHD patients Ok et al. Nephrol Dial Transplant (2011) vol. 26 (4)

52 Cardiovascular outcomes good BP control in both groups, significantly reduced need for antihypertensive medications (22->8%) only in INHD patients improvement in echocardiographic parameters only in the INHD group ( in left atrium and left ventricle end-diastolic diameters, ejection fraction, significant regression of left ventricular mass index) reduction of extracellular fluid documented in a subgroup of the INHD study population by bioimpedance analysis lower progression rate of coronary artery calcification and improvement of arterial stiffness documented in a subset of INHD patients, compared to CHD Ok et al. Nephrol Dial Transplant (2011) vol. 26 (4)

53 Mineral metabolism better phosphate control in INHD patients with reduced use of binders Ok et al. Nephrol Dial Transplant (2011) vol. 26 (4)

54 Nutritional status significantly higher time-averaged levels of serum albumin, triglyceride and cholesterol in the INHD group higher time-averaged interdialytic weight gain in the INHD than the CHD group increase in body weight after 1 year observed only in INDH patients Ok et al. Nephrol Dial Transplant (2011) vol. 26 (4)

55 Anemia and Inflammation significantly higher time-averaged mean Hb level in the INHD group decrease in the percentage of patients on erythropoietin treatment and dose of erythropoietin only in the INHD group lower time-averaged mean CRP levels in the INHD arm after exclusion of patients with a baseline CRP level above 10 mg/dl Ok et al. Nephrol Dial Transplant (2011) vol. 26 (4)

56 Psychometric measurements and QOL memory functions cognitive function Rey Auditory Verbal Learning Test Mini Mental State Examination INHD CHD = = = cognitive function Trail Making Test B = = health-related QOL SF-36 Health Survey = depression/anxiety Hospital Anxiety and Depression Scale = = significant deterioration in the bodily pain, mental health and vitality dimensions Ok et al. Nephrol Dial Transplant (2011) vol. 26 (4)

57 Gender and age distribution of incident HD patients age strata (years)

58 National registry survey of 3702 USA nursing home residents starting dialysis between June 1998 and October 2000 K Tamura et al. N Engl J Med (2009) vol. 361 (16)

59 In conclusion, nursing home residents who are starting to undergo dialysis have a substantial and sustained decline in functional status in addition to very high mortality. K Tamura et al. N Engl J Med (2009) vol. 361 (16)

60 The main aim of my endeavors has always been to restore people to an enjoyable existence. If it s not enjoyable, it should not be done. dr. Willem Johan Kolff