Renal cachexia

Professor Joanne Reid

Cachexia

Cachexia is ‘a complex metabolic syndrome associated with underlying illness and characterised by muscle loss, with or without loss of fat’

Definition of cachexia in chronic illness weight loss of at least 5% within ≤12 months or Body Mass Index (BMI) <20 kg/m2

plus three of the following five features:

• decreased muscle strength;

• fatigue;

• anorexia;

• low fat-free mass index;

• abnormal biochemistry (increased inflammatory markers [CRP, IL-6], anaemia [Hb <120 g/L], low serum albumin [<32g/L] (Evans et al. 2008).

Evans et al. (2008). Cachexia, a new definition. Clinical Nutrition 27,793–799.

Pathogenesis of cachexia

Evans et al. (2008). Cachexia, a new definition. Clinical Nutrition 27,793–799.

Why is it important to investigate cachexia?

• Cachexia is linked with poor outcomes for the patients • Presence of the cachectic syndrome, associated with any chronic disease trajectory, increases

mortality

• Cachexia causes great morbidity, limits therapy

• No standardised ‘best treatment’ for cachexia

• Lack of guidelines / protocols in clinical practice

Living with cancer cachexia: Exploring the perspectives of patients and their significant others

QUB Heritage

Summary findings Summary findings

Conclusions:

•in-depth understanding for patients with cancer and their families

•challenges that they face on a daily basis

•new knowledge on our awareness and comprehension of the experience of

cachexia

Further research: develop interventions that have therapeutic impact for

patients with cachexia and their families

Conclusions

Practice and policy impact

National level - (Royal College of Nursing) Getting it right every time: Nutrition and Hydration Care at end of life (http://rcneolnutritionhydration.org.uk/nutrition-and-hydration/starvation-and-cachexia/).

Thalidomide For Managing Cancer Cachexia

European level - European Society for Clinical Nutrition and Metabolism (ESPEN) ESPEN guidelines on nutrition in cancer patients

Practice and policy impact

BRITISH COLUMBIA INTER-PROFESSIONAL PALLIATIVE SYMPTOM MANAGEMENT GUIDELINES (2017) http://www.bc-cpc.ca/cpc/wp-content/uploads/2017/11/09.-SMG-Clinical-Best-Practices-print-col-anorexia.pdf

Health care professionals’ experience, understanding and perception of need of advanced cancer patients with cachexia and their families: The benefits of a dedicated clinic

Need to develop specialist communication skills training for healthcare professionals Care of patients with cachexia and their families should employ a multi-disciplinary approach

Implications for practice: •A formal educational cancer cachexia programme for clinicians •A dedicated clinic can facilitate a learning environment that allowed best practice to develop across and between professional groups

Study Findings

QUB Heritage Importance of the

problem: renal disease

Importance of problem – renal cachexia?

• Between 30-60% of advanced CKD patients will have cachexia

• Limited attention has been devoted to cachexia in renal disease

• For renal cachexia there are no standardised definitions or inclusion criteria to help inform practice or research

Management of cachexia

• Challenging – definition needs refinement for renal population

• Discriminating cachexia from other causes of malnutrition

• Clinically differentiate between Cachexia and Protein Energy Wasting as each state may require distinct management strategies

Renal cachexia work completed

Belfast based working group established Review paper: Reid et al. (2013). A literature review of end-stage renal disease and cachexia: understanding experience to inform evidence-based healthcare. Journal of Renal Care 39(1), 47–51.

Workshops (funding secured through R&D Office) 1)Belfast to UK working group (BRS conference, 2014) 2)UK to International working group (Belfast workshop, 2014)

Consensus of defining foci and forward planning Editorial: Reid et al (2015) Defining cachexia in a renal population. J of Renal Care 2016 (differentiating between cachexia, sarcopenia and PEW) JHPC. Includes colleagues from UK, USA and Europe

Study funded (Public Health Agency / NI Kidney Research Fund) 1)Establishing a clinical phenotype for cachexia in ESRD – recruitment completed 04/2018 2)Protocol published BMC Nephrology 2018; 19: 38 3)Publish review prior to cross-sectional results JCSM 4)Cross-sectional papers – cachexia / LMM measurement / QoL

Publications Blog: Evidence based nursing: Cachexia and it’s impact on people with renal disease: Posted on December 15, 2014

Establishing a clinical phenotype for cachexia in end stage kidney disease – study protocol Joanne Reid, Helen R. Noble, Gary Adamson, Andrew Davenport, Ken Farrington, Denis Fouque, Kamyar Kalantar-Zadeh, John Mallett, C. McKeaveney, S. Porter, David S. Seres, Joanne Shields, Adrian Slee, Miles D. Witham, and Alexander P. Maxwell doi: 10.1186/s12882-018-0819-3

Reid, J, Noble, HR, Porter, S, Shields, JS & Maxwell, AP 2013, 'A literature review of end-stage renal disease and cachexia: Understanding experience to inform evidence-based healthcare' Journal of Renal Care, DOI: 10.1111/j.1755-6686.2013.00341.x

Reid, J, Noble, H, Davenport, A, Farrington, K, Fouque, D, Porter, S, Seres, D, Shields, J, Slee, A, Witham, MD, Wright, M & Maxwell, AP 2015, 'Defining cachexia in a renal population' Journal of Renal Care, DOI: 10.1111/jorc.12129

Slee A, Reid J (accepted) Wasting in chronic kidney disease: a complex issue. JCSM clinical Reports Reid, J, Noble, HR, Slee, A, Davenport, A, Farrington, K, Fouque, D, Kalantar-Zadeh, K, Porter, S, Seres, D, Withman, MD & Maxwell, AP 2016, 'Distinguishing Between Cachexia, Sarcopenia and Protein Energy Wasting in End-Stage Renal Disease Patients on Dialysis' Palliative Medicine and Hospice Care , vol. 2, no. 2, pp. e11 - e13. DOI: 10.17140/PMHCOJ-2-e004

Working group/Collaborators

• Professor Joanne Reid - QUB

• Dr Helen Noble - QUB

• Professor Sam Porter – Bournemouth University

• Dr Joanne Shields - BHSCT

• Dr Adrian Slee – UCL

• Professor Peter Maxwell - BHSCT / QUB

• Professor Denis Fouque - France

• Professor Ken Farrington – England

• Dr Andrew Davenport - England

• Dr Miles Whitman - Scotland

• Dr David Seres – USA

• Professor Kamyar Kalantar-Zadeh - USA

• Professor Donal O’Donoghue – Manchester University

Belfast Based Team • Current working group

Working group/Collaborators

• Professor Joanne Reid - QUB

• Dr Helen Noble - QUB

• Professor Sam Porter – Bournemouth University

• Dr Joanne Shields - BHSCT

• Dr Adrian Slee – UCL

• Professor Gary Adamson – UU

• Dr John Mallett

• Professor Peter Maxwell - BHSCT / QUB

• Professor Denis Fouque - France

• Professor Ken Farrington – England

• Dr Andrew Davenport - England

• Dr Miles Whitman - Scotland

• Dr David Seres – USA

• Professor Kamyar Kalantar-Zadeh - USA

• Professor Donal O’Donoghue – Manchester University

Belfast Based Team • Current working group

Establishing A Clinical Phenotype For

Cachexia In End-stage Kidney Disease

Background

Aim: The aim of this study is to determine the clinical phenotype of cachexia specific to individuals with ESKD.

Method: This is a longitudinal study which will run over two years.

Recruitment: 106 adult haemodialysis patients using a Regional Nephrology Service in the U.K. with a confirmed diagnosis of stage 5 CKD (beginning dialysis at an estimated GFR <15 mL/min/1.73m2 ).

Data Collection: Patients are followed 2 monthly over 12 months and recorded measurements of weight; lean muscle mass (bioelectrical impedance, mid upper arm muscle circumference - from measures of mid arm circumference and tricep skin fold thickness); muscle strength (hand held dynamometer) and increased inflammatory markers (CRP >5mg/L); anaemia (haemoglobin <120 g/L); low serum albumin (<32g/L). Questionnaires: QoL (KDQoL), Fatigue (FACIT) and Anorexia (FAACT) recorded every two months. Primary renal disease, dialysis vintage and co-morbidities (Charlson Comorbidity Index) were also analysed.

Decreased muscle strength (Dynamometer)

Lean muscle loss (MUA & TSF)

Low albumin

Low Haemoglobin

Increased CRP

Abnormal biochemistry

Fatigue (FACIT) Questionnaire

Anorexia (FAACT) Questionnaire

Baseline findings: primary criteria

<6 patients <20kg/m2

No Weight loss Weight loss (<5% over 6 months or <10% over 12 months) Weight loss (>5% over 6 months or >10% over 12 months)

Average BMI Male Female No Weight loss 29 32 <5% or <10% 24 22 >5% or >10% 23 22

Weight loss of at least 5% ≤6 months or at least 10% ≤12

months

or

Body Mass Index (BMI) <20 kg/m2

Plus three of the following five features:

decreased muscle strength fatigue anorexia low fat-free mass index inflammatory markers (CRP) low serum albumin anaemia

Table 1: Baseline findings (Males)

* *

* significant

Plus three of the following five features:

decreased muscle strength fatigue anorexia low fat-free mass index inflammatory markers (CRP) low serum albumin anaemia

Table 2: Baseline findings (Females)

*

* significant

Table 3: Quality of Life (KDQoL)

Role of primary renal disease, dialysis

vintage and co-morbidities

QUB Heritage Study in collaboration

with EDTNA/ERCA

Research protocol: Awareness, understanding and treatment practices among health care professionals involved in managing cachexia in patients with End-stage kidney disease.

• While progress has been made in exploring the awareness, understanding and treatment practices of health care

professionals who manage cachexia in other chronic illnesses, no study has explored this for cachexia in renal disease

• The importance of this work is underscored by the negative impact that symptoms of cachexia have on quality of life and the association of cachexia with a substantially increased risk of premature mortality

• The study is being conducted with the European Dialysis and Transplant Nurses Association/European Renal Care Association (EDTNA/ERCA)

• The EDTNA/ERCA is a European network established in 1971 to address the educational needs of nurses and other healthcare professionals caring for patients who suffer from Chronic Kidney Disease. EDTNA/ERCA is a multi-disciplinary organisation with membership open to nurses, technicians, social workers, dietitians, unit managers, transplant co-ordinators, and other professionals working with patients with kidney disease.

A STUDY TO GAIN INSIGHTS INTO THE AWARENESS, UNDERSTANDING AND TREATMENT PRACTICES AMONG HEALTH CARE PROFESSIONALS INVOLVED IN MANAGING CACHEXIA IN PATIENTS WITH END STAGE RENAL DISEASE

• Survey – open to all EDNTA / ERCA members

• The information will help us understand the management of cachexia in renal disease.

• Participation is completely anonymous.

• The survey takes approximately 20 minutes to complete.

• Membership with EDTNA/ERCA will not be affected whether you choose to participate or not.

• Return of the questionnaire is considered your consent to participate in this research.

• Click the link below to be taken to the survey or scan the QR code. If you are not able to get to the survey, please copy and paste the link into your internet browser.

• https://tinyurl.com/yaelguoo

• In -depth focus groups

Data collection so far….

• Ongoing – survey remains open 1 focus group to complete

• Survey results so far • Responses from 22 countries worldwide

• Mostly female

• Excellent range of experience in renal speciality (>50% have over 15 years experience)

• Lack of certainty about weight loss associated with cachexia

• Importance of treatment with focus on QoL and family distress

• Need for disease specific definition to facilitate diagnosis and treatment evident

QUB Heritage Renal cachexia research:

next steps

Definition and intervention • A clinical phenotype of cachexia would help to provide early recognition,

prevention and timely-appropriate treatment of this devastating condition.

• Therapeutic approach is dependent on correct classification.

Identify to treat • Develop an intervention to treat cachexia in renal population

• Currently no licensed treatment for cachexia in ESRD

• No accepted standard of care

• Multi-modal intervention • Cachexia is a multifactorial syndrome

• Lends itself to therapeutic targeting through multimodal treatment

Intervention components: Aim - to stop / prevent muscle loss and improve physical function

Optimising food intake has been advocated as a key modality in the treatment of cancer cachexia

Inflammation is one of the main pathophysiological drivers in cachexia. Thus attenuation of the pro-inflammatory response has been argued as a key component of any cachexia therapy.

Qualitative research: enhance person centred care

Qualitative research is able to capture the experience of illness, and enables professionals and providers to understand how individuals perceive illness

Renal cachexia research: Implications

for practice and policy

• Phenomenon continues to be under-recognised and under-treated in clinical practice

•Exploring the awareness, understanding and current treatment practices of renal cachexia is currently underway

•May identify need for similar educational support and development in cancer cachexia

•Clinical trials (robust pharma and non-pharma)

• New knowledge gained from this research will inform and develop future care management strategies in the delivery of evidence-based holistic services to this complex patient population

•Quality Improvement: Implementation of appropriate weight surveillance for clinicians e.g. handgrip strength, BIA?

•Unaddressed holistic difficulties

• Role for education?

Thank You Any questions?