Kidney supportive care: an update of the current state of the art of palliative care in CKD patients

Tavares, Alze Pereira dos Santos; Santos, Cássia Gomes da Silveira; Tzanno-Martins, Carmen; Barros, José; Silva, Ana Maria Misael da; Lotaif, Leda; Souza, Jonathan Vinicius Lourenço

doi:10.1590/2175-8239-JBN-2020-0017

Alze Pereira dos Santos Tavares Correspondence to: Alze Pereira dos Santos Tavares. E-mail: alze.tavares@santapaula.com.br

Sociedade Brasileira de Nefrologia, Comitê de Cuidados Paliativos, São Paulo, SP, Brasil.

Hospital Santa Paula, São Paulo, SP, Brasil.

https://orcid.org/0000-0003-0783-0106

Cássia Gomes da Silveira Santos

Sociedade Brasileira de Nefrologia, Comitê de Cuidados Paliativos, São Paulo, SP, Brasil.

Universidade Federal do Paraná, Hospital das Clínicas, Curitiba, PR, Brasil.

Carmen Tzanno-Martins

Sociedade Brasileira de Nefrologia, Comitê de Cuidados Paliativos, São Paulo, SP, Brasil.

Clínica de Hemodiálise, São Paulo, SP, Brasil.

https://orcid.org/0000-0002-7839-1828

José Barros Neto

Sociedade Brasileira de Nefrologia, Comitê de Cuidados Paliativos, São Paulo, SP, Brasil.

Sociedade Brasileira de Nefrologia Mineira, Belo Horizonte, MG, Brasil.

Felício Rocho Hospital, Departamento de Nefrologia, Belo Horizonte, MG, Brasil.

Ana Maria Misael da Silva

Sociedade Brasileira de Nefrologia, Comitê de Cuidados Paliativos, São Paulo, SP, Brasil.

Leda Lotaif

Sociedade Brasileira de Nefrologia, Comitê de Cuidados Paliativos, São Paulo, SP, Brasil.

Instituto Dante Pazzanese de Cardiologia, Nefrologia e Hipertensão e Pós-Graduação, São Paulo, SP, Brasil.

HCor, São Paulo, SP, Brasil.

Jonathan Vinicius Lourenço Souza

Sociedade Brasileira de Nefrologia, Comitê de Cuidados Paliativos, São Paulo, SP, Brasil.

HCor, São Paulo, SP, Brasil.

Correspondence to: Alze Pereira dos Santos Tavares. E-mail: alze.tavares@santapaula.com.br

AUTHOR’S CONTRIBUTION

All authors contributed equally to this work.

CONFLICT OF INTEREST

All authors declare that they have no conflict of interest related to the publication of this manuscript.

Strategy	Action
Management of symptoms and quality of life	Evaluate symptoms on a regular basis with the use of validated tools and adopt effective measures for control
Prognostic	Evaluate prognosis on a regular basis with the use of validated tools
Communication	Establish a patient-centered communication and explore patient values and preferences
Shared decision making	Promote shared decision-making on renal replacement therapy options, including dialysis and non-dialytic control of chronic kidney disease
Advance care planning	Explore patient values and preferences in advance about unwanted health care when they lose the ability to make decisions for themselves and realistic life goals they would like to achieve. Advance directives of will are part of this process
Comprehensive conservative care	Evaluate, select, and provide comprehensive conservative care to individuals who are unlikely to benefit from dialysis
Patient-centered dialysis	Personalize treatment and deliver it with dignity, compassion, and respect to the patient values and preferences
Incremental hemodialysis	Implement incremental HD according to the metrics of residual kidney function to reduce the burden of treatment
Palliative dialysis	Implement palliative or “comfort” dialysis and tailor it to individual patient needs to optimize quality of life and minimize burden of treatment
Dialysis withdrawal	Develop written guidelines on how and when to discuss dialysis withdrawal and how to manage patients after withdrawal
End-of-life care	Explore patient preferences for end-of-life care when life expectancy is less than 12 months

Instrument	Population	Number of symptoms	Time to complete	Recall period	Frequency of symptom	Impact of symptom on HRQoL
ESAS-r: Renal	Dialysis	10	NR	Present	N	N
IPOS-Renal	Non-dialysis	15	< 10 min	1 week	N	N
DSI	Dialysis	30	NR	1 week	N	N
CKD-SBI	Dialysis and Non-dialysis	32	NR	4 weeks	Y	Y
KDQOL-36^* * Instrument used to evaluate HRQoL;	Dialysis and Non-dialysis	30	> 30 min	4 weeks	Y	Y^ Only for pain, sexual dysfunction, sleep and fatigue. Abbreviations: ESAS-r: Renal, Edmonton symptom assessment system-revised: Renal; IPOS-Renal, integrated palliative care outcome scale-renal; DSI, dialysis symptom index; CKD-SBI, chronic kidney disease-symptom burden index; KDQOL, kidney disease quality of life instrument; HRQoL, health-related quality of life; Y, yes; N, no; NR, not reported.

Symptom	Medication	Comments
Pain	1. Mild pain (1-3) - Dipyrone or Paracetamol (max. of 3g daily) 2. Moderate pain (4-6) - Tramadol with reduced dose. On dialysis 50-100mg 2x / d (maximum dose). In conservative 5-50mg 2x / d (maximum dose). Some authors recommend skip step 2 in CKD. 3. Severe Pain (7-10) - Fentanyl, Buprenorphine, Hydromorphone and Methadone are considered safe. Start with small doses.	Assess the cause of pain. Reduction of 20-30% in pain intensity is sufficient to improve HRQoL. Administer analgesic medication according to WHO principles: by mouth, by the clock, by the ladder, for the individual and with attention to detail. Neuropathic or mixed pain requires another class of medications as SSRI, TCAs, and Gabapentinoids.
Uremic pruritus	Gabapentin CKD stage 3 and 4 – start with 50-100 mg 1 – 2 h before sleep CKD stage 5 – start with 100mg on alternate nights Dialysis – start with 100mg after each session and holder for efficacy and side effects	Remove other causes of pruritus. Moisturizing is advisable.
Restless legs syndrome	Gabapentin - as above Dopaminergic agonist - ropinirole 0.5mg at night or pramipexole 0.25mg at night If the patient presents with uremic pruritus and cramp prefer gabapentin	If the patient has uremic pruritus and cramps, prefer gabapentin.
Nausea and vomiting	First line: ondansetron 4 – 8 mg every 8 h as needed. Second line: Metoclopramide 2.5 every 8 h as needed and before meals. Third line: olanzapine 2.5 mg every 8 h as needed or haloperidol 0.5 mg every 8 h as needed.	Multifactorial in origin. Metoclopramide acts as a central and peripheral antiemetic (uremic and diabetic gastroparesis).
Constipation	Bisacodyl or Senna	Add fiber to diet. Check for medications that cause constipation.
Dyspnea	Hydromorphone - start at 0.5mg 4x / d and increase if tolerated Morphine 2.5mg 4x / day for 2 to 3 days	Exclude reversible causes
Anorexia	Remove precipitants Diet review Supplements	Multifactorial
Fatigue	Treat the reversible causes	Multifactorial
Anxiety	Counseling Psychologist / Psychiatrist evaluation If panic attack consider Benzodiazepines - Lorazepam 0.5mg to 1mg.	Multifactorial
Depression	Some SSRIs as Citalopram, Fluoxetine and Sertraline are safe for use in CKD	Difficult to diagnose because the symptoms of depression seem those of the DRCT. Consider Psychiatrist evaluation.
Sleep disturbance	Assess the cause carefully Treat the cause Temazepam 10-20 mg at night	If sleep apnea is suspected - polysomnography

Tool	Feature
1. The Surprise Question (SQ): "Would you be surprised if this patient died in the next 12 months?"	A simple and useful tool to identify patients at greater risk of death. Applicable at any stage of CKD.⁶⁰60 Javier AD, Figueroa R, Siew ED, Salat H, Morse J, Stewart TG, et al. Reliability and utility of the surprise question in CKD stages 4 to 5. Am J Kidney Dis. 2017 Jul;70(1):93-101.
2. AKPS (Australia-modified Karnofsky Performance Status scale) or KPS (Karnofsky Performance Scale)	Tools used to assess the patient's functional status. A patient with AKPS or KPS of less than 50% is eligible for palliative care. That is, a patient who, due to one or more chronic diseases, spends at least 50% of the time sitting or lying down, without considering sleep time.⁶¹61 Abernethy AP, Shelby-James T, Fazekas BS, Woods D, Currow DC. The Australia-modified Karnofsky Performance Status (AKPS) scale: a revised scale for contemporary palliative care clinical practice. BMC Palliat Care. 2005;4:7.
3. Modified Charlson score (MCS)	A tool that adds comorbidities scores (9 in total) to age scores (an additional point for each decade above the age of 40) to identify patients on dialysis with a higher risk of death.⁶²62 Hemmelgarn BR, Manns BJ, Quan H, Ghali WA. Adapting the Charlson comorbidity index for use in patients with ESRD. Am J Kidney Dis. 2003 Jul;42(1):125-32.
4. Fried Phenotype Model	Frailty is highly prevalent in CKD and associated with increased risk of hospitalization and mortality.⁶³63 Chowdhury R, Peel NM, Krosch M, Hubbard RE. Frailty and chronic kidney disease: a systematic review. Arch Gerontol Geriatr. 2017 Jan/Feb;68:135-42.
5. Bansal Score	This tool uses nine clinical variables (age, sex, race, eGFR, albumin / creatinine ratio, diabetes, smoking, heart failure and stroke) to estimate the risk of death at 5 years in the elderly (≥ 70 years) with non-dialytic DRC (stages 3 and 4).⁶⁴64 Bansal N, Katz R, Boer IH, Peralta CA, Fried LF, Siscovick DS, et al. Development and validation of a model to predict 5-year risk of death without ESRD among older adults with CKD. Clin J Am Soc Nephrol. 2015 Mar;10(3):363-71.
6. REIN Score	REIN Score Instrument validated to stratify the risk of death in 3 months of elderly patients (> 75 years) who intend to initiate dialysis⁶⁵65 Couchoud CG, Beuscart JB, Aldigier JC, Brunet PJ, Moranne OP, REIN registry. Development of a risk stratification algorithm to improve patient-centered care and decision making for incident elderly patients with end-stage renal disease. Kidney Int. 2015 Nov;88(5):1178-86.
7. Cohen 6-month Mortality Predictor (available at: http://touchcalc.com/calculators/sq)	An instrument that combines SQ with four variables - age, serum albumin, presence of dementia and peripheral vascular disease - to predict the risk of death at 6, 12, or 18 months for hemodialysis patients.⁶⁶66 Cohen LM, Ruthazer R, Moss AH, Germain MJ. Predicting six-month mortality for patients who are on maintenance hemodialysis. Clin J Am Soc Nephrol. 2010 Jan;5(1):72-9.
8. KDIGO Clinical Outcomes in CKD (available at: https://kdigo.org/equation/)	This tool estimates concomitantly the risks of death, RRT, and any cardiovascular disease in 2 and 4 years in patients with CKD with eGFR between 15 and 30 mL/min/1.73m2 and aged between 30 and 85 years.

Issue	Current Disease-Focused Metrics for Conventional Dialysis Care	A Patient-Centered and Palliative Approach to Dialysis Care
Vascular access	Creation and maintenance of an AV fistula	CVC is acceptable
Dialysis adequacy	Target small solute clearance based on current standards (Kt/V.1.2 for HD and Kt/V.1.7 for PD), intensifying the dialysis prescription as needed to achieve targets	Lower clearance acceptable if changes prescription increase demands inconsistent with patient preference. Taylor dialysis to minimize symptoms and treatment burden.
Cardiovascular disease	Treat CV risk factors, potentially targeting BP and dyslipidemia	Tolerate hypertension to avoid symptoms; limited use of medication to treat hypertension and dyslipidemia treatment
Mineral and bone disorder	Dietary counseling; binders to control hyperphosphatemia; vitamin D analogues with or without calcimimetics for secondary hyperparathyroidism	Limited restrictions; more permissive hyperphosphatemia and hyperparathyroidism
Nutrition	Encourage dietary protein intake while limiting potassium (if HD), sodium, and phosphorus intake	Dietary restrictions only to mitigate symptoms and improve quality of life.
Laboratory monitoring	Routine monthly laboratory tests	Minimal necessary
Drugs	Prescribed for treatment and prevention	Prescribed primarily to improve HRQoL or symptoms relief
Anemia management	IV iron and ESAs to achieve targets for Hb and TSAT/Ferritin	IV iron and ESAs only as needed
Symptom management	Only as needed	In a regular base

Symptom	Intervention
Nausea and vomiting	Haloperidol SC 0,5 to 1.0 mg 8 hourly
Nausea and vomiting	Levomepromazine SC 2.5 to 5 mg hourly
Respiratory secretions	Hyoscine butilbromide SC 20 mg, hourly as required (up to 120 mg in 24h)
Anxiety and distress	Midazolam SC 2 mg as required hourly
Anxiety and distress	Lorazepam sublingual 0.5 mg 8 hourly as required
Dyspnea	Fentanyl 25–50 µg subcutaneous 2 hourly as required (first choice)
	Morphine 1.5–2.5 mg sub subcutaneous cut 2 hourly as required
	Diuretic (if applicable), ventilator (in face), and relaxation techniques
Delirium	Haloperidol 0.5 mg to 2 mg 8 hourly
Terminal agitation	Midazolam SC 10 to 20 mg over 24 h plus midazolam SC 5 mg hourly, as required

[1] Correspondence to: Alze Pereira dos Santos Tavares. E-mail: alze.tavares@santapaula.com.br

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Kidney supportive care: an update of the current state of the art of palliative care in CKD patients

ABSTRACT