Options in Renal Replacement Therapy: When, whom, which? Prof Dr. Serhan Tuğlular Marmara University Medical School Division of Nephrology

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1 Options in Renal Replacement Therapy: When, whom, which? Prof Dr. Serhan Tuğlular Marmara University Medical School Division of Nephrology

2 CKD Classification Stage Description GFR (ml/min/1.73.m2) 1 Kidney damage with normal or GFR 2 Kidney damage with mild GFR > Moderate GFR Severe GFR Kidney failure < 15 or dialysis

3 When to start dialysis? KDOQI US 2004 EBPG Europe 2002/2011 CARI Australia 2004 CSN Canada 1999 UK Guidelines 2002 Renal Kt/V urea/week <2 (Opinion) Renal Kt/V urea of 2.0 corresponds to a GFR of 10.5 ml/min/1.73m2 GFR< 15ml/min + symptoms GFR<9 6ml/min/1.73m2 GFR<10ml/min/1.73m2 +symptoms GFR<6mL/min/1.73m2 GFR<12ml/min/1.73m2 +symptoms GFR<6mL/min/1.73m2 Renal Kt/V urea/week <2 (GFR 14ml/min) +symptoms GFR of 12 ml/min corresponds to Ccreat of 18ml/min or renal Kt/V of 2.0

4 What are these symptoms? Malnutrition Inability to control hydration status or BP Uremic signs & symptoms Nausea/vomiting Loss of apetite Pericarditis Uremic lung Cognitive impairment Peripheral Neuropathy and others. If nutritional state and hydration control is good and no uremic signs present Initiation can be postponed until GFR <6mL/min/1.73m2

5 Initiating Dialysis Early and Late (IDEAL) study Pts >18 years CC ml/min/1.73m2 1.Group:CC ml/min/1.73m2 (EARLY) 2.Group:CC 5 7 ml/min/1.73m2 (LATE) N Engl J Med 2010;363: Pts in either group start dialysis based on clinical indications Mean follow up : EARLY : n= 404; 3.64 years LATE: n= 424; 3.57 years 76% of the patients in the late group started dialysis with CC higher than 7 ml/min/1.73m2, the majority due to uraemic symptoms. The average CC at the time of starting dialysis was : EARLY: 12.0 ml/min/1.73m2 LATE: 9.8 ml/min/1.73m2 Late group started dialysis on average 6 months later than the early group.

6 Does early start decrease survival? N=23551 incident HD pts egfr*, ml/min/1.73 m2: Q1: 2.6 Q2: 3.8 Q3: 4.7 Q4: 5.8 Q5: 7.7 Low rate of mortality during the first year of dialysis (13.2/100 patient years) Higher egfr at dialysis initiation to be associated with increased mortality risk Nephrol Dial Transplant (2010) 25:

7 N= pts; İn center HD in US; No comorbidity: no DM;No > 65 years 1 egfr 2 plasma albumin: a surrogate for unmeasured morbidity egfr Persons With Albumin Level 3.5 g/dl (n=35 665) HR P value < <0.001 > <0.001 Starting e GFR has little effect on survival of the sicker pts; Among fitter pts starting e GFR relative increase in mortality Arch Intern Med. 2011;171(5):

8 2011 EBPG Position Statement 3 High risk patients e.g. diabetics and those whose renal function is deteriorating more rapidly than egfr 4 ml/ min/year : 1. Require particularly close supervision. 2. Where close supervision is not feasible and in patients whose uraemic symptoms may be difficult to detect, a planned start to dialysis while still asymptomatic may be preferred (1C Strong recommendation based on low quality evidence).

9 2011 EBPG Position Statement 4 Asymptomatic patients presenting with advanced CKD: May benefit from a delay in starting dialysis in order to allow preparation, planning and permanent access creation rather than using temporary access (2C Weak recommendation based on low quality evidence)

10 Decision making more complex for older and more fragile patients Physiological benefits of Solute clearance ECF volume control Physical risks Psychosocial toll of therapy The initiation of dialysis therapy remains a decision informed by clinical art, as well as by science and the constraints of regulation and reimbursement

11 Predialysis education Patients with CKD stage 4 (estimated GFR < 30 ml/min/1.73 m 2 ) timely education about kidney failure and options for its treatment Kidney transplantation PD HD (in the home or in center, and conservative treatment) Patients' family members and caregivers also should be educated about treatment choices for kidney failure.

12 O P T I O N S I N R R T Hemodialysis Peritoneal Dialysis Transplantation Conventional (in-center) HD Home HD Living Donor CONTINUOUS AMBULATORY PERITONEAL DIALYSIS (CAPD) AUTOMATED PERİTONEAL DİALYSİS ( Deceased Donor S (APD) APD) Nocturnal HD Short Daily HD Preemptive Kidney-Pancreas

13 N Engl J Med 1999;341: J Am Soc Nephrol 12: , 2001 Which is the Best? Annual Death Rate/100 pt years Transplant pts Waiting List pts At 3 4 years (RR : 0.32 P<0.001) Improved survival with Tx Diabetics, African Americans, All age groups Inc. 60 to 74 years old.

14 Am J Kidney Dis 2010; 55(Suppl 1):Ch6 S

15 Transplantation offers the best survival rate for patients with ESRD Am J Kidney Dis 2010; 55(Suppl 1):Ch6 S

16 2008 Annual Report

17 Transplantation in Elderly patients Survival still better than Dialysis

18 Mortality rate decreases in all dialysis patients from except those ESRD pts on Dialysis for >5years have significantly increased death rates Am J Kidney Dis 2010; 55(Suppl 1):Ch6 S

19 A survival advantage with less time on the transplant waiting list

20 671 first, preemptive, kidney only transplantations egfr MDRD (ml/min/1.73m2 ): Grup 1: <10.0 Grup 2: Grup3: >15.0 Grup 1 vs Grup3 posttx: 1.Week GFR 6.3mL/min/1.73m2 2. YearGFR 4.5 ml/min/1.73m2 RR for graft failure :0.99

21 Advantages and Disadvantages of Transplantation Advantages A better quality of life Increased survival Less expensive Productivity restored Freedom from dialysis Fewer, if any, diet and fluid restrictions. Feeling better physically. No longer seeing themselves as chronically ill. Disadvantages Risk of a major surgery Bleeding Infection Damage to surrounding organs Life long immunosupression Adverse effects of medications Increased risk of malignancy Increased risk of Infection

22 Advantages and Disadvantages of Preemptive Transplantation Advantages Protection from Dialysis related complications: Catheter infection Hepatitis Better pt. and graft survival rates No need for vascular access Protection from sensitization Less admission to hospital Disadvantages Decreasing the time to use native kidney function (>14ml/dk TX) Returning to dialysis in case of graft dysfunction Increase in organ demand Noncompliance

23 Who is Eligible for transplantation and Who isn t? Eligible Most patients with kidney failure at ages 2 70 due to Glomerulonephritis Chronic pyelonephritis (VUR) Hereditary Metabolic Obstructive nephropathy Toxic Multisystem diseases HUS Tumors Congenital Irreversible ARF Not eligible (Absolute CI) Disseminated or untreated cancer Severe psychiatric disease Unresolvable psychosocial problems Persistent substance abuse Severe mental retardation Un reconstructable coronary artery disease or refractory congestive heart failure

24 Furthermore. Some diseases may recur in renal transplants : IgA nephropathy Focal segmental glomerulosclerosis Membranous glomerulonephritis Membranoproliferative glomerulonephritis Amyloidosis Cystinosis Relative contraindications: Treated malignancy Substance abuse history Chronic liver disease Cardiac disease Structural GU abnormality or recurrent UTI Past psychosocial abnormality Aortailiac disease

25 Further problems: Sensitized recipient RETRANSPLANT BLOOD TRANSFUSİON HIGH PRA Kidney International, Vol. 58 (2000), pp

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28 Current Status of RRT in the world 1,222, , ,000 1,783,000 World Population: 6,919,586,519

29 The Choice Between HD and PD Availability Convenience Comorbid conditions Home situation Age The ability to tolerate volume shifts Residual renal function Preference of the physicians

30 For Conventional In Center HD PROS Treatments are standardized three treatments per week, four days off Always under surveillance of trained professionals Obesity less of a problem Less malnutrition Less need for Hospital admission CONS Pt must travel to the center for treatment. Anemia more prevalent than PD Hemodynamic and other complications during treatment AV fistula problems Risks for blood borne infection (hepatitis) More expensive in most countires

31 For Peritoneal Dialysis PROS Lower cost than HD (in most countries) Pts more satisfied with overall care compared to HD Steady state treatment. Better tolerated hemodynamically Needleless Preservation of vascular sites for future HD Lower risk of blood borne infections (hepatitis, ect.) Alleviates anxiety for needle sticks Better preservation of RRF Fewer diet and fluid restrictions Less EPO use /no heparin Freedom to work, to go to school ect. CONS Continuous therapy. No days off Body image concerns High technique failure rates compared to HD Space needed for monthly supplies of dialysis equipment and solutions Non compliance may lead to complications İnfections/uremia/ technique failure

32 Which is better for whom? Favors PD Full time work Pediatric patients Women with small children Good family support Well motivated Pts with better chance for tx Unable to travel to the facility Needs to travel a lot PTS with VA problems Favors HD Poor family support Not motivated for self care Severe comorbidity Obesity >110kg Poor hygiene, poor self care Poor Manual dexterity Abdomen not suitable for PD

33 Home Hemodialysis PROS Flexible times More control over times to dialyze, No travel to dialysis clinic for treatment More independent Access via the phone (or clinic appointment) to a nurse, dietitian and social worker to answer questions or to solve problems CONS Not all facilities offer home hemodialysis Pt and partner will need to be trained for several weeks for home hemodialysis Need room for storage of equipment and supplies Need to call paramedic for help in an emergency Home must have required plumbing and electrical capabilities

34 Alternative HD Schedules Short daily HD hr/session, 5or >days/week Daily nocturnal HD 6 10 hr/session, 5 or > days/week Long intermittent HD 8 hr, 3 days or nights/week PD+HD combination therapy Patients able to learn to perform their own HD at home may eventually be able to use frequent HD regimens Hemodialysis International 2006; 10:

35 Choices for Healthy Outcomes in Caring for ESRD (CHOICE) Time Point Relative risk of death 95% CI Year Year Patients stratified by age and diabetes at baseline, no difference in mortality was seen by dialysis modality Those with residual urine output at baseline did not have an increase in mortality with PD,,while those without residual renal function did.

36 PD patients had less severe comorbidity, this relationship persisted after controlling for all other factors associated with modality selection Am J Kid Dis, Vol 39, No 2 (February), 2002: pp

37 Effects of comorbid and demographic factors on dialysis modality choice and related patient survival in Europe Seven European renal registries participating in the ERA EDTA Registry provided data from incident peritoneal dialysis (PD) and haemodialysis (HD) pts ( ) The likelihood to receive PD rather than HD 3 year survival on PD versus HD Nephrol Dial Transplant (2011)0: 1 8

38 Elderly patients patients with PVD, CD, malignancy and multiple comorbidities were significantly less likely to receive PD than HD. Nephrol Dial Transplant (2011)0: 1 8

39 Effects of comorbid and demographic factors on dialysis modality choice and related patient survival in Europe Overall pts starting on PD Had survival benefit Esp. Pts without comorbidities And with malignancy Nephrol Dial Transplant (2011)0: 1 8

40 Similar Outcomes With Hemodialysis and Peritoneal Dialysis in Patients With End Stage Renal Disease Arch Intern Med. 2011;171(2):

41 PD vs HD PD Age<65years No cardiovascular disease No diabetes >90 days after initiation No difference in survival HD With CVD & DM Cum. survival Probability Months PD HD p J Am Soc Nephrol 21: , 2010

42 Outcomes in patients on home haemodialysis in England and Wales, : a comparative cohort analysis Home HD patients were more likely to be white, less likely to be socially deprived, less likely to have higher risk primary renal diseases more likely to be put on the waiting list for kidney transplantation had higher baseline serum albumin Home HD pts have Better survival rates than in center HD and PD Nephrol Dial Transplant (2011) 26:

43 THE INTEGRATED CARE CONCEPT HD and PD are complementary modalities The better preservation of RRF Lower risk of infection with hepatitis B and C Better outcome after transplantation Preservation of vascular access Lower costs PD a good initial treatment When PD related problems arise: Adequacy & UF failure Peritonitis Patient burnout A timely transfer to HD J Am Soc Nephrol 11: , 2000

44 THE INTEGRATED CARE CONCEPT Patients initially treated with PD who subsequently switched to HD had improved survival as compared with those who started with and remained on HD 1 Intention to treat survival and total survival were not different between PD and HD patients Of the patients who remained on their initial modality for more than 48 months, PD patients had reduced survival as compared with their matched HD counterparts J Am Soc Nephrol 11: , 2000

45 A reformulated version of integrated care Hemodialysis International 2006; 10:

46 CONCLUSION GFR and uremic signs and symptoms, including malnutrition should be considered when starting the patient on dialysis Transplantation is the best method of RRT Preemptive transplantation must be considered where possible Patients who are not eligible for preemptive tx should receive timely, adequate and unbiased education regarding the complete array of RRT options available, including home based PD and HD HD and PD does not seem to have a survival benefit over each other They must be considered as complementary modalities and an Integrated care should be planned

47 Thank you