Conservative management of advanced chronic kidney disease in primary care setting

Opening Vignette

Mrs. Tan is an 85-year-old grandmother who visits the polyclinic for routine follow-up of her chronic conditions. She has underlying diabetes mellitus (DM), hypertension and hyperlipidaemia for the past 20 years. You notice that her estimated glomerular filtration rate (eGFR) has been falling by 3 mL/min/1.73 m² per year over the last 3 years and she now has stage 4 chronic kidney disease (CKD) with an eGFR of 20 mL/min/1.73 m². Her DM and hypertension are well controlled with glycated haemoglobin (HbA1c) of 6.9% and average blood pressure (BP) of 110/80 mmHg. She does not smoke or drink alcohol. Mrs. Tan is independent in her activities of daily living and enjoys walking as a form of exercise. She usually comes to the clinic unaccompanied and is adherent to her medications and follow-ups. You have been advising her about the risk of kidney failure requiring dialysis and to visit a nephrologist. However, Mrs. Tan has refused, as she feels well and does not wish to burden her son with her care or adhere to a dialysis schedule. She asks if she could continue follow-up at the polyclinic, as it is convenient for her.

WHAT IS ADVANCED CKD?

Chronic kidney disease (CKD) is defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m² for 3 months or more, irrespective of cause. Kidney disease severity has been classified into five stages according to the level of GFR and degree of albuminuria/proteinuria. Advanced CKD includes stages 4 and 5 of the CKD classification, with an eGFR <30 mL/min/1.73 m².

HOW RELEVANT IS THIS TO MY PRACTICE?

In Singapore, the prevalence of CKD was reported to be 15.6% in 2007. This is projected to increase to 24.3% by 2035.[1] The rise is contributed by our ageing population as well as increasing prevalence of diabetes mellitus (DM) and hypertension.[2]

Advanced CKD is associated with many complications. Dialysis discussion and planning are usually initiated at CKD stage 4. However, for patients who are older, frail and have multiple comorbidities, it is unclear whether dialysis improves health or survival. There is evidence to suggest that dialysis can negatively impact the quality of life and functional status in certain subsets of patients, who will instead benefit more from conservative kidney management (CKM).[3,4] Efforts should be focused on slowing CKD progression and optimising quality of life via shared decision-making and promoting patient values and preferences with implementation of advance care planning (ACP) and coordinated palliative care.[5]

After formal review by a nephrologist and decision for CKM, this group of patients will benefit from shared care between primary care physicians and specialists. There are also patients who decline nephrology referrals but continue chronic disease management with their primary care providers. Therefore, it is important for primary care physicians to be familiar with the principles of nondialytic management of advanced kidney disease.[6] This article focuses on patients with CKD stage 4 or 5 who are conservatively managed.

WHAT CAN I DO IN MY PRACTICE?

Slowing progression of kidney disease

Optimising diabetes and hypertension care

In developed countries, DM and hypertension are the leading causes of CKD, especially in the elderly.[7] In Singapore, 70% of new cases of end-stage kidney disease (ESKD) are attributed to DM.[8] Various guidelines differ with regards to recommendations about target haemoglobin A1c (HbA1c) in CKD. The KDIGO (Kidney Disease Improving Global Outcomes) clinical practice guideline is commonly used in our local practice. An HbA1c of 7%–7.5% is suitable for most patients with advanced CKD,[7] but this should be individualised, especially for individuals with comorbidities and limited life expectancy, where a higher HbA1c target of 8%–8.5% is likely to be acceptable. Metformin should be stopped when eGFR falls below 30 mL/min/1.73 m² (CKD stage 4 and 5). It is not recommended to start sodium–glucose transport protein 2 (SGLT2) inhibitors if eGFR is <25 mL/min/1.73 m², but these drugs can be continued till stage 5 CKD if initiated earlier in the course of CKD.

Similarly, there is considerable variation in the target blood pressure (BP) suggested by various guidelines. For managing elderly frail patients suitable for CKM, we suggest a target BP <140/90 mmHg, and this can be lowered to <130/80 mmHg if tolerated.[7]

Optimising CKD care

Patients that have CKD are often on renin–angiotensin system blockade, including angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs), with the aim to reduce proteinuria and slow the decline in kidney function. In patients with CKD stage 4, ACE-I/ARBs can still be continued; however, a 25% dose reduction may be considered in patients with hyperkalaemia or rapid eGFR decline (>4 mL/min/1.73 m² per year). When eGFR is <15 mL/min/1.73 m², ACE-I or ARBs should be discontinued.

Patients who have proteinuric CKD (with or without DM) will benefit from treatment with SGLT2 inhibitors. According to the DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial,[9] dapagliflozin reduced adverse renal and cardiovascular outcome by 39%. As mentioned above, it is not recommended to start SGLT2 inhibitors if eGFR is <25 mL/min/1.73 m².

Lifestyle changes

Nutritional therapy can delay CKD progression and facilitate better management of complications such as electrolyte and acid–base imbalances, water and salt retention, mineral bone disorders and failure to thrive. Studies suggest that a reduced protein intake helps to slow CKD progression and lower urea production. A very low protein diet (<0.6 g/kg/day) with supplementation of essential amino acids or their ketoacids (e.g., ketosteril) may be beneficial for select patient groups. Dietary sodium restriction also helps to control BP and reduce fluid retention. However, sodium restriction has not been established to slow CKD progression.[10]

The following are recommended for patients with advanced CKD:[11] (a) maintain a protein intake of 0.8 g/kg/day and sodium intake of <2 g/day; (b) undertake moderate-intensity physical activity for a cumulative duration of at least 150 min/week, or at a level compatible with their cardiovascular and physical tolerance, where possible; and (c) stop smoking, as smoking is associated with a more rapid decline in kidney function, and cardiovascular disease, the primary cause of mortality in this patient population.

Medication review

Patients’ medication list should be regularly reviewed, with dose adjustments considered based on renal function. These patients may develop increasing gout flares as their CKD progresses.[11] Patients should be advised to avoid nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors. When appropriate, urate-lowering therapy should be considered.

Managing complications of advanced CKD

Patients with advanced CKD can develop multisystem complications. Table 1 shows the investigations and recommended screening intervals.

Table 1.

Recommended screening blood test intervals for patients with CKD stage 4 or 5.[8]

Test	Frequency, monthly
	Stage 4b	Stage 5b
Full blood count	6	6
Kidney function testa	4	1–3
Calcium/phosphate	3–6	1–3
Parathyroid hormone	6–12	3–6

The suggestions are for reference. The frequency of tests should be individualised based on the magnitude of abnormalities and the rate of progression of chronic kidney disease (CKD). ^aKidney function test includes testing for urea, creatinine, sodium, potassium and bicarbonate. ^bEstimated glomerular filtration rate for CKD stage 4 and 5 is <30 mL/min/1.73 m² and <15 mL/min/1.73 m², respectively.

Anaemia

Advanced CKD is associated with anaemia, especially when eGFR falls below 30 mL/min/1.73 m². Anaemia is defined as Hb <13 g/dL in males and <12 g/dL in females, but in patients with advanced CKD, the target is to maintain an Hb of at least 10 g/dL. Patients with advanced CKD should undergo a full blood count test at least twice a year. Those with anaemia should undergo further evaluation for serum iron, folate and vitamin B₁₂ levels. Ferritin level of >500 ng/mL and transferrin saturation (Tsat) level of >20% should be maintained in this group with oral iron supplementation.

Erythropoiesis-stimulating agents can be used to maintain adequate Hb levels. This reduces the requirement for blood transfusions and improves the quality of life and exercise capacity. Commonly used recombinant erythropoietin preparations include Recormon (epoetin beta), Aranesp/Nesp (darbepoetin alfa) and Mircera (methoxy polyethylene glycol-epoetin beta), which are administered subcutaneously. For patients who are on recombinant erythropoietin, the Hb levels should be checked at least every 4 months.

Metabolic acidosis

Chronic kidney disease is associated with metabolic acidosis, which can lead to increased bone loss, CKD progression, hypoalbuminaemia and insulin resistance. Multiple studies have suggested that serum bicarbonate levels <22 mEq/L are associated with adverse outcomes, including the risk of CKD progression, bone demineralisation, skeletal muscle catabolism and increased risk of death, whereas serum bicarbonate levels >28 mEq/L are associated with vascular calcification and increased risk of death.[12,13] Patients can be started on PO sodium bicarbonate at a dose of 500 mg BD (serum bicarbonate 19–21 mEq/L) or 1 g BD (serum bicarbonate <18 mEq/L) to achieve a normal serum bicarbonate level of >22 mEq/L. The dose can be titrated monthly up to a dose of 1 g TDS. It is important to avoid exceeding serum bicarbonate concentrations >29 mEq/L, since this has been associated with increased mortality in patients with CKD.[7]

Hyperkalaemia

Patients with advanced CKD are at risk of developing hyperkalaemia. They should be on a low-potassium diet and avoid medications that raise serum potassium concentration. The ACE-Is/ARBs may need to be discontinued in persistent hyperkalaemia. In conservatively managed patients who have refractory hyperkalaemia, physicians can prescribe regular sodium polystyrene sulfonate up to three times a week. Other agents like sodium zirconium cyclosilicate (commonly known as Lokelma) are also available in Singapore and can be prescribed by nephrologists for patients who are unable to tolerate sodium polystyrene sulfonate due to gastrointestinal side effects.

Fluid overload

Patients with advanced CKD are prone to fluid overload. These patients generally respond to the combination of dietary sodium restriction (<2 g/day) and diuretic therapy. It is advisable for patients to keep a weight diary; this can provide guidance on the range of ideal weight to maintain and titration of diuretics. Patients are often on a regular dose of diuretics, usually frusemide, up to a maximum dosage of 120 mg TDS. For patients with advanced CKD and refractory volume overload, thiazide-like diuretics (e.g., metolazone) can be used in addition to loop diuretics for short intervals of 2–3 days.

Mineral and bone disorders

The following is suggested: (a) screen serum calcium and phosphate every 3–6 months and (b) check serum 25-hydroxyvitamin D levels and correct any deficiency and insufficiency with treatment strategies recommended for the general population. Phosphate retention is common in CKD patients. Dietary phosphate restriction and oral phosphate binders may limit the development of secondary hyperparathyroidism. Calcium-based phosphate binders can be titrated to target normophosphataemia. The two commonly available phosphate binders are calcium acetate and calcium carbonate. Patients may also be started on non-calcium-based phosphate binders (lanthanum or sevelamer). Patients should be advised to take phosphate binders with meals.

Preventive health

Patients with CKD are at increased risk for developing infections. Adults with advanced CKD should be vaccinated with influenza, coronavirus disease 2019, pneumococcal conjugate and polyvalent pneumococcal vaccines, unless contraindicated.[7]

Palliative care in advanced CKD

Shared decision-making is a process where a healthcare professional works closely with a patient to reach an informed healthcare decision. This involves discussion and information sharing of risks, benefits and possible consequences of various options, with consideration of the patient’s preferences, beliefs and values. This empowers patients to make decisions about the care and treatment that would be in line with their goals of care at that time.

Comprehensive conservative care for kidney failure focuses on slowing the decline in renal function, actively managing symptoms, ACP and the provision of appropriate palliative care.[5,11] Advance care planning is a national programme that serves as a platform that enables conversations between the patients and their caregivers, wherein their goals, values, preferences for treatment and care are discussed. This is essential as many advanced CKD patients on conservative pathway feel well despite worsening eGFR and do not think they have a serious life-limiting illness. These patients are prone to acute deterioration and becoming acutely symptomatic. If in-house ACP programmes are not available in the primary care institution, patients can be referred to any of the ACP providers in Singapore (https://www.aic.sg/care-services/acp-directory).

Estimating prognosis

Unlike patients with underlying malignancy, prognostication of conservatively managed ESKD patients is challenging, with a median survival ranging from 6 months to 2 years.[14] Therefore, reviews at regular intervals are required to monitor disease trajectory and symptoms. There are multiple prognostic tools available to assist clinicians in predicting mortality in this group. Some examples are ‘Predicting 6- and 12-Month Mortality in CKD patients calculator’ and ‘The Gold Standards Framework Centre in End-of-Life Care 2011’.

Basic palliative care can be provided by primary healthcare physicians. Palliative care aims to improve the quality of life of patients with life-limiting illness and their families through the prevention and relief of suffering. However, if patients are symptomatic (including functional decline), clinicians can consider referral to home hospice care or specialist palliative review. There is a range of hospice services available in Singapore [Table 2]. If deemed suitable, clinicians can apply for hospice services via the Agency for Integrated Care (AIC) platform. Patients and their families can also indicate a preference on the choice of hospice care facility, considering factors such as location and the services provided.

Table 2.

List of different hospice services available in Singapore.

Hospice service	Criteria	Services provided
Hospice Day Care Centre	• Community care (able to walk/mobilise in wheelchair)	• Physiotherapy, occupational therapy, art/music therapy
	• Life-limiting illness	• Recreational activities (e.g. music, art and craft, grooming, cooking, outings)
		• Pain and symptom control
		• Psychosocial and spiritual support
		• Respite care in the day
Hospice Home Care	• Homebound care	• Pain and symptom control
	• Prognosis <12 months	• Psychosocial and spiritual support
		• End-of-life care
		• Caregiver training
		• Equipment loan
		• 24-h coverage with hotline and after-office hour visits as needed
Inpatient Hospice	• Inpatient care	• Pain and symptom control
	• Prognosis <3 months	• Psychosocial and spiritual support
		• Respite care
		• End-of-life care

Terminal care in ESKD patients

Patients with advanced CKD have extensive palliative care needs for years before death. Throughout the illness trajectory, their symptom burden is often high. The following are the common symptoms and the suggested management.[15]

Pain

Common causes of pain in advanced CKD include renal osteodystrophy, peripheral neuropathy, peripheral vascular disease, ischaemic heart disease and calciphylaxis. Where possible, we suggest treating the underlying cause of pain, e.g., good wound care in the case of pain related to ulcers or use of appropriate medications for neuropathy. Otherwise, pain control should be guided by the World Health Organisation pain ladder: (a) mild: paracetamol, (b) moderate: tramadol (dose adjusted if creatinine clearance [CrCl] is 10–30 mL/min; maximum 50–100 mg BD; avoid if CrCl <10 mL/min), (c) severe: fentanyl is the opioid of choice in CKD; morphine is excreted renally and should be avoided in patients with advanced CKD; opioid may still be used in small doses (when necessary) at longer intervals, and (d) adjuvants: gabapentin/pregabalin will require dose adjustment.

Nausea/vomiting or constipation

Treatment of these symptoms is the same as for the general population. Haloperidol is the drug of choice for nausea associated with uraemia. Metoclopramide can be used in cases of stasis or obstruction impeding gastric emptying, frequently seen in diabetic patients. However, it would be prudent to avoid laxatives that require lots of fluids, such as Fybogel. Diuretics can also be titrated based on the fluid status, as poor oral intake or vomiting can lead to dehydration, which in turn, worsens uraemia and its symptoms.

Dyspnoea

Patients with ESKD often experience dyspnoea contributed by anaemia, fluid overload, acidosis and anxiety. Physicians should try and treat the reversible causes where appropriate. Patients with hypoxia may be offered oxygen supplementation. Nonpharmacological measures, such as good air circulation, respiratory physiotherapy and occupation therapy, may provide some relief. The accumulation of secretions in the respiratory tract is a common complication for these patients near the end of life. Fluid restriction helps decrease secretion production and reduces discomfort. N-butylscopolamine bromide (Buscopan) decreases secretion production and can be administered subcutaneously at the end of life. Pharmacological measures include treatment with opioids.

Itch

Patients with advanced CKD often experience itch. This can be contributed by uraemia, hyperphosphataemia, iron deficiency and dry skin. Nonpharmacological measures to relieve itch include water-based emollients or other adjuncts such as phototherapy and acupuncture. If required, pharmacological measures can be used. Antihistamines do not decrease uraemic pruritus, but the sedative properties can be helpful with sleep disorders. Other agents that have been described include gabapentin/pregabalin, serotonin (5-hydroxytryptamine type 3) and selective serotonin reuptake inhibitors.

Anxiety

For anxiety or agitation, anxiolytics, mainly benzodiazepines, may be prescribed.

Pill burden

Advanced CKD patients are found to have an average of 11 types of medications, and this is associated with a lower quality of life and nonadherence. In patients with an estimated prognosis of <3 months, we recommend a review of medications with a view to reduce pill burden as priority changes. Diuretics should be continued in most patients to alleviate symptoms associated with volume overload.

WHEN SHOULD I REFER TO A SPECIALIST?

Shared care model involves collaboration among practitioners of different skills and knowledge or disciplines to deliver healthcare tailored to the patient’s needs. In the management of advanced CKD, this would involve primary healthcare physician, nephrologists and palliative care physicians.

Patients with advanced CKD should be referred to nephrology, especially if there is no previous CKD evaluation and renal replacement therapy (RRT) discussion or a rapid decline in eGFR by >5 mL/min/1.73 m² per year.[7] The decision about dialysis versus CKM is complex and dependent on various factors such as the patient’s wishes, comorbidities, functional status and prognosis. It is advisable to refer to a nephrologist for initial evaluation unless patients explicitly state their decision for CKM and refuse nephrology review. A nephrologist can assist with medical optimisation of anaemia, acidosis and hyperphosphataemia and initiate treatment for secondary hyperparathyroidism in appropriate cases. The patients can then be discharged or comanaged with primary care physicians.

As the patient progresses from advanced CKD to ESKD, it is crucial to involve the palliative care physician when indicated, especially if the patient’s physical symptoms are becoming difficult to manage or psychological, social and spiritual support is required. Supplemental Digital Appendix shows a summary of the management of CKD.

TAKE-HOME MESSAGES

1. Comprehensive CKM refers to planned, holistic patient-centred care for patients with advanced CKD that focuses on slowing CKD progression and optimising quality of life via shared decision-making and promoting patient values and preferences.

2. Comprehensive CKM is an appropriate treatment option for advanced CKD patients with multiple comorbidities and frailty.

3. Patients with advanced CKD often have a high symptom burden, and these symptoms should be assessed and managed accordingly.

4. Patients with advanced CKD on CKM will benefit from shared care between primary care physicians and specialist care (nephrology and palliative as indicated).

5. Palliative care services are available for patients being managed in the community and are available via the online AIC platform.

Closing Vignette

Over a family conference, you discuss Mrs. Tan’s advanced CKD and its expected trajectory with her family, and counsel them on her treatment options, including RRT and CKM. Mrs Tan shares that she does not wish to pursue RRT and hopes to avoid hospitalisations. Her family wants to respect her wishes and focus on the goal of comfort. You refer her for ACP. Six months later, Mrs. Tan’s eGFR falls below 15 mL/min/1.73 m². She has worsening dyspnoea and finds it difficult to leave her house for medical appointments. You stop her nonessential medications and refer her to the home hospice service.

Conflicts of interest

Goh LH is a member of the SMJ Editorial Board and was thus not involved in the peer review and publication decisions of this article.

Supplemental digital content

Appendix at http://links.lww.com/SGMJ/A161

SMC CATEGORY 3B CME PROGRAMME

Online Quiz: https://www.sma.org.sg/cme-programme

Deadline for submission: 6 pm, 14 February 2025

Question: Answer True or False
1. Advanced chronic kidney disease (CKD) refers to a sustained estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 for at least 3 months.
2. Dialysis can help to prolong survival in patients with end-stage kidney disease (ESKD), and so complications of dialysis should not be discussed.
3. Glycated haemoglobin and blood pressure targets should be individualised for patients with advanced CKD.
4. Metformin is contraindicated in a patient with an eGFR of <30 mL/min/1.73 m2.
5. If patients are already on sodium-glucose transport protein 2 inhibitors, this medication must be stopped if their eGFR falls to <30 mL/min/1.73 m2.
6. Angiotensin-converting enzyme inhibitor/angiotensin receptor blockers increase the risk of hyperkalaemia in patients with declining renal function even if they have been on the same dose for many years.
7. Smoking is associated with a more rapid decline in kidney function.
8. Chronic kidney disease is an indication for initiation of urate-lowering therapy in patients with gout.
9. A 70-year-old lady with advanced CKD was found to have a haemoglobin level of 9 g/dL. She should be started on recombinant erythropoietin without further evaluation.
10. Metabolic acidosis is common in patients with advanced CKD.
11. Dose reduction of vitamin D replacement is required when treating vitamin D deficiency in patients with advanced CKD, in view of impaired renal function.
12. Pneumococcal and influenza vaccinations are contraindicated in patients with CKD due to their immunocompromised state.
13. Advance care planning (ACP) is a national programme, and patients can be referred to any of the ACP providers in Singapore.
14. Patients with eGFR <30 mL/min/kg should be referred to nephrology for discussion of renal replacement therapy only if they are symptomatic.
15. There is no role for nephrology follow-up in patients with advanced CKD who opted for conservative kidney management.
16. Patients with advanced CKD can have extensive palliative care needs for years before death.
17. Patients with ESKD have similar illness trajectory as patients with cancer.
18. Opioids can be used to manage dyspnoea in patients with ESKD on conservative kidney management.
19. Nonpharmacological interventions are ineffective and have no role to play in managing dyspnoea in patients with ESKD.
20. Palliative care referral may be considered if the patient’s physical symptoms are becoming difficult to manage or psychological, social and spiritual support is required.

Table S1.

Summary of suggestions for management of chronic kidney disease (CKD)

Management of advanced CKD
Slowing CKD progression Lifestyle changes including smoking cessation, daily salt / protein intake, exercise Systolic blood pressure target <130mmHg and HbA1c target 7-7.5% as tolerated Manage proteinuria with ACE-I/ARB or SGLT-2 inhibitors as renal function allows Patient safety Review medication list based on renal function	CKD complications				Preventive health Influenza, pneumococcal and COVID-19 vaccinations Advance care planning (ACP) Offer ACP discussion and refer accordingly Consider referral to relevant hospice services When to refer + co-manage • Nephrology CKD4 and above No previous CKD evaluation No previous RRT discussion • Palliative Prognosis <12months Symptomatic (physical, psychological, social, or spiritual)
	What to monitor	How often	Target	Action to take
	Fluid status	3 months	Eu-volemia	Salt and fluid restriction Review medications
	Hb	4-6 months	10-12 g/dL	Screen and treat for other causes of anaemia Refer to Nephrology to start erythropoiesis-stimulating agent
	Kidney function test	1-3 months	Normal limits	If eGFR declines by >5 mL/min/1.73m2 per year, refer to Nephrology
				If K>6 mmol/L, review diet and medications. If persistent, refer to Nephrology.
	Serum bi-carbonate	1-3 months	>22 mmol/L	Start sodium bicarbonate
	Serum calcium, phosphate	1-6 months	Normal limits	Replace Vit D if deficient. If serum phosphate level is high, restrict dietary phosphate intake and start phosphate binders

Funding Statement

Nil.