The Old Paradigm (The full cup) Fistula First Utilize Kt/V for “adequate” dialysis 3 – 4 hours, thrice weekly Manage ASCVD “Optimize” treatment: anemia (EPO and Iron), divalent ions (phosphate binders), PTH (Vitamin D), lipids, BP control, estimate “dry weight” Restrictive diets Early Start

The State of Renal Care in the U.S. Challenges and Changes “We can do better” Dallas, Texas June, 2010

The Boston Steering Committee Conclusions The model of dialytic care since the 1970s is insufficient: –the nephrology community likely used incomplete - perhaps even flawed – science, at least as we know the science now –the providers and payers supported the model –for 35 years. The problem is propagated by how we measure ourselves: –Clinical Performance Measures; (CPMs; CPGs; i.e., HGB, Kt/V, Ca, P, …) Though enormously helpful, current CPMs do not provide the power to predict the outcomes that we had hoped for, either for the patient or the facility. Current CPMs account for only about 14% of the measurable differences in facility outcomes (SMRs). Consequentially, too many patients are dying, hospitalizations are too high, and cost is enormous. The Boston meeting concluded that now we have the information to change this

To accomplish: The REASONS for the Boston Meeting –Mortality trends –Hospitalization trends –Costs SUMMARY of Boston Meeting data, conclusions and recommendations ACTIONS to implement change, since the meeting

Mortality

Dallas M and M Conference

The Boston meeting concluded that – now – we can do better than this.

Hospitalizations

The Boston meeting concluded that we can do something about this.

Once again, it was concluded that we can do something about this.

Costs

$34B if other payors included

Our Current Milieu of Care 20% of facility patients die each year; 70% deceased in 5 years; Up to 40% mortality in the first year A program that costs $34+,000,000,000/year With a cost of $60 – 80,000 PPPY with the difference based on AV access alone $20,000 PPPY in hospitalizations, mostly due to cardiovascular disease and infection Less than 20% rehabilitation 110,996 new ESRD patients – 2007 –101,688 In Center HD –6506 PD (6875 in 2005) –2665 Pre-emptive transplant (2424 in 2005)

Therapies and Outcomes Results from an informal survey at 2008 ASN Possible Therapies –CAPD –CCPD –Conventional In Center –Nocturnal In Center –Conventional HHD –Nocturnal HHD –Short Daily HHD –Transplant Living Cadaveric –Palliative Therapies Stratified by Nephrologists’ Choice –Transplantation –Nocturnal HHD –Nocturnal In-center and Short Daily HHD –Conventional HHD –CAPD and CCPD –Conventional In Center –Palliative

98% would choose alternatives to conventional care. If we are going to choose conventional therapy for patients, then we need to do it better. Let’s at least get it right.

To Accomplish This Morning The REASONS for the Boston Meeting –Mortality –Hospitalization trends and causes –Costs A SUMMARY of Boston Meeting data, conclusions and recommendations ACTION since the meeting

Primary Issues Identified (4 days, >1700 PPT Slides) Infection and AV Access Cardiovascular Disease Inflammation The Dialysis Dose The First Year

82%

Catheter Events and Hospitalizations Fistula events and complication are.2 to.4 as prevalent

Consequences of Catheters 22% infectious complications, with septic arthritis, endocarditis and osteomyelitis 43% higher cardiovascular related death rate than fistulas in some studies AVF after 90 days with 29% reduction in all- cause mortality compared to catheters Greater all cause and infection related hospitalizations Reduced dialysis adequacy, poorer quality of life and greater costs

Infection Trends Infection hospitalizations substantially increasing over past 10 years, largely due to catheters Infection hospitalizations increasing at a rate greater than cardiovascular hospitalizations Much higher costs in patients with catheters There is even likely a linkage between one access infection and associated ongoing risk of death Higher mortality in catheter patients and facilities with more catheters (and grafts)

Boston Meeting Recommendations #1: Infection and Access Acknowledge: The catheter problem is IATROGENIC Hospitals, health plans, nephrologists, providers and vascular surgeons (currently, 50% primary failure rate) must be accountable for reducing catheter placement CMS might consider moving catheters, as a CPM, to the very highest level of scrutiny and surveys and place less emphasis on CPMs that make little difference in outcomes –They just concluded a TEP to make just such recommendations, which are now being considered Vaccination, as a CPM, needs to be an important aspect of facility practice and accountability

Primary Issues Infection and AV Access Cardiovascular Disease Inflammation The Dialysis Dose The First Year

ASCVD is apparently not the leading cause of CV death, and all of these years we’ve concentrated on hemoglobin, calcium, phosphorus, lipids and the like – to fix the cardiovascular problem. We’ve simply been looking at the wrong outcomes measures to improve mortality, hospitalizations and cost associated with CV disease.

It’s LVH and Cardiomyopathy glassock % LVH

THEME: Alterations in LV Mass in CKD/ESRD are an Example of What is WRONG with Conventional Regimens of Treatment

The Core Issues: LV Disease LV mass disease progresses as CKD progresses (not inevitably) Increased LV Mass is very prevalent in the incident ESRD patient (70%), with only minimal to modest improvement with conventional in-center HD (A bit better with PD) Non regressors have a very poor prognosis Glassock

Three of every four deaths and hospitalizations in dialysis patients can be linked to sudden death or CHF Glassock Left Ventricular in Origin

Ritz

Ritz

Leading Causes of LV Muscle and Fibrotic Disease Hypervolemia –“dry weight” is an “evil doer” –Whatever happened to euvolemia or normalized extracellular volume? Hypertension Inflammation (likely caused by hypervolemia) Cardiac stunning during overly aggressive ultrafiltration because of shortened dialysis

Volume Overload and LVH In experimental spontaneous hypertension, LV Mass increase is linked to volume expansion and salt intake, not to blood pressure Salt-loading may increase LV mass through local effects (augmentation of A- II effects and TGFβ) (Varagic J. et al Am J Physiol Heart Circ Physiol 290:Hi503, 2006; Wu HCM, et al Circulation 98:2621, 1998) )

Consequences of LVH and cardiac fibrosis CHF –Difficulty attaining euvolemia with short Rx time –Because of ongoing hypervolemia, it is the leading cause of hospitalizations and death, especially in the first year, but ongoing. –High cause of re-hospitalization Arrhythmias –Fibrous tissue encircling myocytes with high electrical resistance; local delay of the spreading front of the action potential Favors “re-entry” type of atrial and ventricular ARRYTHMIAS with high hospitalization and death

LVH and Dialysis mode and Prescription Conventional 3x/wk dialysis corrects less than 40% of LVH Observational (cross-sectional) studies show a lower prevalence of LVH in PD compared to conventional HD patients Emerging data: More frequent/longer HD sessions: strongly associated with a much lower prevalence, even reversal of LVH compared to conventional HD (Awaiting FHN studies) It is very difficult to attain euvolemia with the current model of care

What has not worked so far in conventional hemodialysis to resolve cardiovascular disease? Statins have not been effective –4D and Aurora ESA treatment of anemia has not had a salutary effect on mortality Attempting to attain euvolemia with conventional HD Traditional outcome assessments oriented towards ASCVD Sodium modeling and control

LVH in ESRD: Effect of EPO therapy Seven (7) RCT have been conducted that examine the effect of EPO therapy on LVH in CKD/ESRD All but one have failed to show any beneficial effect on LVH of EPO therapy and correction of hemoglobin to normal or near normal levels

Harmful Effect of Dialysis (after McIntyre CW, et al CJASN, 4:914,2009) Myocardial “Stunning” (transient regional wall motion abnormality) develops frequently (65%) during hemodialysis, especially in presence of underlying CHD and/or Diabetes High UF volumes increase risk Repeated episodes compromise cardiac function, lead to LV fibrosis and enhance mortality risk

Sodium Known effects on blood pressure and hypervolemia (inter-dialytic weight gains) Blood pressure independent target organ damage –Vasculature changes –Minor increases of sodium in CSF or serum increases pressor mechanisms and increases cardiotonic steroids – sodium modeling And we load our patients with sodium –Hypertonic Saline bolus for hypotension –Saline bolus in the rinse back (hypertonic) and priming –Sodium modeling –Dialysate sodium (hypertonic to usual serum sodium)

A New Paradigm Adding control of LVH to Clinical Performance Guidelines will achieve salutary effects on morbidity and mortality in ESRD therapy

Cardiovascular Disease in ESRD: Boston Conclusions This is a problem of the left ventricle, not ASCVD It is a problem of hypervolemia The new paradigm of ESRD therapy must include modification of LVH as a high priority Current “conventional” HD regimen is insufficient to fully correct or substantially modify LVH by lowering extracellular volume, BP and correcting fibrosis (despite “adequate” Kt/V), in the majority of patients Longer/more frequent HD regimens with shorter inter- dialytic intervals very likely improve LVH (and thereby reduce hospitalizations and mortality due to CHF and arrhythmias) - FHN will provide the definitive answer

Boston Meeting Recommendations #2: Cardiovascular (LV) Disease Forego misapplication of the formulaic (Kt/V) approach to “adequate” dialysis Greater emphasis on LV disease with Td tied to attainment of normalized ECV (not “dry weight). Td and volume become the new CPMs. Caution about sodium modeling until safety studies affirm benefit (Did not recommend more frequent or hugely longer therapies. Though tying therapy to volume removal will likely result in somewhat longer therapies.) CMS to work with nephrology community in development of objective measures for assessment of volume status that would result in decreased hospitalization costs induced by volume/CHF/LVH/arrhythmias –They just concluded a TEP to do just that

Primary Issues Infection and AV Access Cardiovascular Disease Inflammation The Dialysis Dose The First Year

Reversing “Inflammation- Induced” Malnutrition Dietary counseling, in the traditional manner, has minimal effect Dietary supplements have mixed effect IDPN does not have sustainable effect More frequent and/or longer therapy has the greatest effect in reversing the problem

Boston Meeting Recommendations #3: Inflammation No infection from catheters Abandon the “renal diet” as a universal approach to nutritional counseling, except Na Attain normovolemia Feed patients, even nutritional supplements, and then give them more than conventional dialysis to remove K, P, etc. (The “renal diet” seems to have served the renal community, rather than the patient, by allowing the patient to look biochemically intact, while we give inadequate dialysis.) So, no catheters, more food and more dialysis (Note the emerging same story)

Primary Issues Infection and AV Access Cardiovascular Disease Inflammation The Dialysis Dose The First Year

The Dialysis Dose The history and methodologies about our current dosing are flawed and not supported by current science It was a model developed over 30 years ago, propagated by nephrologists, the payment system and dialysis providers And no longer sustainable Too many patients are going into the hospital, are dying, with the associated high costs The misapplication of Kt/V is highly detrimental

Lowrie And this totally ignores volume removal

Effect of Other Therapies Td and Interval Alan Kliger Daily (Suri et al)Outcomes# of Studies SBP or MAPDecrease10 of 11 P or Binder DoseNo Change6 of 8 AnemiaImprovement7 of 11 AlbuminIncrease5 of 10 QOLImprovement5 of 10 Nocturnal (Walch) LV MassImprovementCulleton SBP or MAPDecrease4 of 4 HBP MedicationsDecrease4 of 4 AnemiaImprovement3 of 3 QOLImprovementVariable

The Four Major Problems with Kt/V In and of itself, it may not be “bad”. It is simply not enough Does not acknowledge the differences in therapies required for size of the individual Does not acknowledge the disproportionate value of TD (duration of treatment time per week) Does not account for the fact that most dialysis patients, using conventional Kt/V, are not euvolemic, but indeed are volume overloaded

Boston Meeting Recommendations #4: Dialysis Prescription Kt/V is not the “Holy Grail” and has enormous shortcomings Time on dialysis needs to become a CPM, tied to: – LV disease –Euvolemia, not “dry weight” –blood pressure –inter-dialytic weight gain Work with CMS to develop CPMs acknowledging this with the goal to fix CV disease –They have just concluded a TEP to address this very issue

Primary Issues Infection and AV Access Cardiovascular Disease Inflammation The Dialysis Dose The First Year

Hakim

Hakim

Boston Meeting Recommendations #5: Incident Patients They need more intensive care, by the nephrologist and dialysis provider, and directed at those co-morbid processes that cause the greatest mortality, hospitalizations, re-hospitalizations and costs: catheters and infection, volume overload, wound care, malnutrition...

Primary Issues Infection and AV Access Cardiovascular Disease Inflammation The Dialysis Dose The First Year

Dialysis: The Old Paradigms Fistula First Optimize kT/V Manage Coronary Heart Disease “Optimal” treatment: anemia (EPO and Iron), divalent ions (phosphate binders), PTH (Vitamin D), lipids, BP medications, albumin Restrictive diets Early Start

Dialysis: The New Paradigm Catheter last Volume control first, minding the left ventricle More dialysis with emphasis on time Emphasis on the incident patient Eat, eat, eat (but not salt)

Conclusions for this Network 14 Meeting After 1711 slides and 4 days in Boston The Boston Meeting is not suggesting that we discard existing CPMs. CPMs and CPGs are a rigorous and thoughtful process. The emphasis on traditional CPMs needs to be changed and new CPMs need to be added. And that we be held more accountable for better outcomes

Specific Conclusions for this RPA Meeting: After 1711 slides and 4 days in Boston Cease to spend so much time on weaker clinical outcomes measurements that may only account for 14% of the morbidity and mortality difference. Change the CPMs Save the left ventricle and gain optimal control of volume. Change the CPMs Do not tolerate catheters or those who place them. Change the CPMs Intensify the care of the incident patients. Do not be satisfied with a formulaic approach to conventional dialysis. Change the CPMs (Partially treat inflammation with more protein and caloric intake and time on dialysis)

I’m asking that, when you leave here today, that you: Challenge your prior perceptions of adequate dialysis, time on dialysis and euvolemia and implement change. –Patients should attain normal ECV the first of the week. If not, schedule more time or an extra treatment that week. Abandon all catheters > 90 days in incident patients Intensify care of incident patients Feed your patients more protein, then give them sufficient dialysis

To accomplish: An very brief overview of current ESRD data –Mortality –Hospitalization trends and causes –Costs A SUMMARY of Boston Meeting data, conclusions and recommendations ACTION since the meeting and in the future

Action Since Boston Meeting Letter to CMS and White House Meeting with CMS, November – 2009 and follow-up calls CJASN Supplement, December – 2009 Articles in NNI and RenalWeb ASN 2009 – 2 hour session RPA 2010 ANNA 2010 Numerous Medical Schools and other venues ASN 2010 Recent CMS Technical Expert Panel Mtg: March Upcoming studies

CMS and Volume Held a meeting in Baltimore, , a Technical Expert Panel to address the volume component of adequacy of dialysis Recommendations –All patients start at 4 hours –Greater sodium control No sodium modeling Lower dialysate sodium concentration –Required clinical assessment of volume –Home BP monitoring –Pending: objective measurement

Recent CMS Regulation and Reporting Change New data reporting for adequacy, infection and vascular access beginning July 1, 2010 –Purpose: To develop “quality incentive payment for dialysis providers” by January 1, 2012 Indicators –Kt/V –Access infection –Type of access

The world is changing. The old ways will not do. It’s time… John Kennedy