Latest Guidance Updates
November 2022: updates to the sections on top takeaways for clinicians, comprehensive care, glycaemic monitoring and targets, lifestyle interventions, and glucose-lowering therapies. This update includes five updated algorithms, and new sections on sodium–glucose cotransporter-2 inhibitors and mineralocorticoid receptor antagonists.
This Guidelines summary includes actionable recommendations for the management of type 1 and type 2 diabetes (T1D and T2D) in chronic kidney disease (CKD).
It includes guidance on comprehensive care, glycaemic monitoring and targets, lifestyle and glucose-lowering interventions, and approaches to self-management and optimal models of care.
Reflecting on your Learnings
Reflection is important for continuous learning and development, and a critical part of the revalidation process for UK healthcare professionals. Click here to access the Guidelines Reflection Record.
Grades of Recommendation
This summary includes a mix of recommendations and ‘practice points’ to help clinicians better evaluate the guidance. Practice points are clearly labelled throughout the summary.
Within each recommendation in this summary, the strength of the recommendation is indicated as level 1 or 2, and the quality of the supporting evidence is shown as A, B, C, or D:
|Level 1—recommended||Most patients should receive the recommended course of action|
|Level 2—suggested||Different choices will be appropriate for different patients. Each patient needs help to arrive at a management decision consistent with her or his values and preferences|
|Grade||Quality of Evidence||Meaning|
|A||High||The guideline authors are confident that the true effect is close to the estimate of the effect|
|B||Moderate||The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different|
|C||Low||The true effect may be substantially different from the estimate of the effect|
|D||Very low||The estimate of effect is very uncertain, and often it will be far from the true effect|
Top Takeaways for Clinicians
|Box 1: Diabetes Management in Chronic Kidney Disease—Top Takeaways for Clinicians|
1. Comprehensive Care
Patients with diabetes and CKD have multi-system disease that requires treatment including a foundation of lifestyle intervention (healthy diet, exercise, weight management, no smoking) and drug therapy that improves kidney and cardiovascular outcomes (glucose, lipids, blood pressure).
2. Nutrition Intake
Patients should consume a balanced, healthy diet that is high in vegetables, fruits, whole grains, fibre, legumes, plant-based proteins, unsaturated fats, and nuts; and lower in processed meats, refined carbohydrates, and sweetened beverages. Sodium (<2 g/day) and protein intake (0.8 g/kg/day) in accordance with recommendations for the general population should be followed.
3. Sodium–Glucose Cotransporter-2 Inhibitors
Sodium–glucose cotransporter 2 inhibitors (SGLT2i) should be initiated for patients with T2D and CKD when estimated glomerular filtration rate (eGFR) is ≥20 ml/min/1.73 m2 and can be continued after initiation at lower levels of eGFR. SGLT2i markedly reduce risks of CKD progression, heart failure, and atherosclerotic cardiovascular diseases, even when blood glucose is already controlled.
Metformin should be used for patients with T2D and CKD when eGFR is ≥30 ml/min/1.73 m2. For such patients, metformin is a safe, effective, and inexpensive drug to control blood glucose and reduce diabetes complications.
5. Glycaemic Monitoring and Targets
Haemoglobin A1c (HbA1c) should be measured regularly. Reliability decreases with advanced CKD, particularly for patients treated with dialysis, and results should be interpreted with caution. Continuous glucose monitoring (CGM) or self-monitoring of blood glucose (SMBG) may also be useful, especially for treatment associated with risk of hypoglycaemia. Targets for glycaemic control should be individualised, ranging from <6.5% to <8.0%.
6. Glucagon-like Peptide-1 Receptor Agonists
In patients with T2D and CKD who have not achieved individualised glycaemic targets despite use of metformin and SGLT2i, or who are unable to use those medications, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) is recommended as part of the treatment.
7. Renin–Angiotensin System Blockade
Patients with T1D or T2D, hypertension, and albuminuria (persistent albumin-to-creatinine [ACR] >30 mg/g) should be treated with a renin–angiotensin system inhibitor (RASi) (angiotensin-converting enzyme inhibitors [ACEi] or angiotensin II receptor blockers [ARB]), titrated to the maximum approved or highest tolerated dose. Serum potassium and creatinine should be monitored.
8. Non-steroidal Mineralocorticoid Antagonists
Non-steroidal mineralocorticoid antagonists (ns-MRA) reduce risks of CKD progression and cardiovascular events for people with T2D and residual albuminuria. They are suggested for patients with T2D, urine ACR ≥30 mg/g, and normal serum potassium on other standard of care therapies. Serum potassium and creatinine should be monitored.
9. Approaches to Management
A team-based and integrated approach to manage these patients should focus on regular assessment, control of multiple risk factors, and structured education in self-management to protect kidney function and reduce risk of complications.
Comprehensive Care in Patients with Diabetes and CKD
Algorithm 1: Kidney–Heart Risk Factor Management
Comprehensive Diabetes and CKD Management
- Practice point: Patients with diabetes and CKD should be treated with a comprehensive strategy to reduce risks of kidney disease progression and cardiovascular disease (see Algorithm 1 and 2).
Algorithm 2: Holistic Approach for Improving Outcomes in Patients with Diabetes and CKD
- Recommendation, 1B: It is recommended that treatment with an ACEi or an ARB be initiated in patients with diabetes, hypertension, and albuminuria, and that these medications be titrated to the highest approved dose that is tolerated
- Practice point: For patients with diabetes, albuminuria, and normal blood pressure, treatment with an ACEi or ARB may be considered
- Practice point: Monitor for changes in blood pressure, serum creatinine, and serum potassium within 2–4 weeks of initiation or increase in the dose of an ACEi or ARB (see Algorithm 3)
- Practice point: Continue ACEi or ARB therapy unless serum creatinine rises by more than 30% within 4 weeks following initiation of treatment or an increase in dose (see Algorithm 3)
- Practice point: Advise contraception in women who are receiving ACEi or ARB therapy and discontinue these agents in women who are considering pregnancy or who become pregnant
- Practice point: Hyperkalaemia associated with the use of an ACEi or ARB can often be managed by measures to reduce serum potassium levels rather than decreasing the dose or stopping the ACEi or ARB immediately (see Algorithm 3)
- Practice point: Reduce the dose or discontinue ACEi or ARB therapy in the setting of either symptomatic hypotension or uncontrolled hyperkalaemia, despite the medical treatment outlined in the practice point immediately above, or to reduce uremic symptoms while treating kidney failure (estimated glomerular filtration rate (eGFR) <15 ml/min per 1.73 m2)
- Practice point: Use only one agent at a time to block the RAS. The combination of an ACEi with an ARB, or the combination of an ACEi or ARB with a direct renin inhibitor, is potentially harmful.
Algorithm 3: Monitoring of Serum Creatinine and Potassium During ACEi or ARB Treatment—Dose Adjustment and Monitoring of Side Effects
- Recommendation, 1A: Treat patients with T2D, CKD, and an eGFR ≥20 ml/min per 1.73 m2 with an SGLT2i
- Practice point: The recommendation for SGLT2i is for kidney and cardiovascular protection and SGLT2i have been shown to have safety and benefit in CKD patients, even for those without T2D. Thus, if patients are already being treated with other glucose-lowering agents, an SGLT2i can be added to the current treatment regimen (see Algorithm 4)
- Practice point: The choice of an SGLT2i should prioritise agents with documented kidney or cardiovascular benefits and take eGFR into account
- Practice point: It is reasonable to withhold SGLT2i during times of prolonged fasting, surgery, or critical medical illness (when patients may be at greater risk for ketosis)
- Practice point: If a patient is at risk for hypovolaemia, consider decreasing thiazide or loop diuretic dosages before commencement of SGLT2i treatment, advise patients about symptoms of volume depletion and low blood pressure, and follow up on volume status after drug initiation
- Practice point: A reversible decrease in the eGFR with commencement of SGLT2i treatment may occur and is generally not an indication to discontinue therapy
- Practice point: Once an SGLT2i is initiated, it is reasonable to continue an SGLT2i even if the eGFR falls below 20 ml/min per 1.73 m2, unless it is not tolerated or kidney replacement therapy is initiated.
Algorithm 4: Practical Provider Guide to Initiating SGLT2i in Patients with T2D and CKD
Mineralocorticoid Receptor Antagonists
- Recommendation, 2A: An ns-MRA is recommended, with proven kidney or cardiovascular benefit for patients with T2D, an eGFR ≥25 ml/min per 1.73 m2, normal serum potassium concentration, and albuminuria (≥30 mg/g [≥3 mg/mmol]) despite maximum tolerated dose of RASi
- Practice point: ns-MRA are most appropriate for patients with T2D who are at high risk of CKD progression and cardiovascular events, as demonstrated by persistent albuminuria despite other standard-of-care therapies
- Practice point: An ns-MRA can be added to a RASi and an SGLT2i for treatment of T2D and CKD
- Practice point: To mitigate risk of hyperkalaemia, select patients with consistently normal serum potassium concentration and monitor serum potassium regularly after initiation of an ns-MRA
- Practice point: The choice of an ns-MRA should prioritise agents with documented kidney or cardiovascular benefits
- Practice point: A steroidal MRA should be used for treatment of heart failure, hyperaldosteronism, or refractory hypertension, but may cause hyperkalaemia or a reversible decline in glomerular filtration, particularly among patients with a low GFR.
- Recommendation, 1D: Advise patients with diabetes and CKD who use tobacco to quit using tobacco products
- Practice point: Physicians should counsel patients with diabetes and CKD to reduce second-hand smoke exposure.
Glycaemic Monitoring and Targets in Patients with Diabetes and CKD
- Recommendation, 1C: The use of HbA1c to monitor glycaemic control in patients with diabetes and CKD is recommended
- Practice point: Monitoring long-term glycaemic control by HbA1c twice per year is reasonable for patients with diabetes. HbA1c may be measured as often as four times per year if the glycaemic target is not met or after a change in antihyperglycemic therapy
- Practice point: Accuracy and precision of HbA1c measurement declines with advanced CKD, particularly among patients treated by dialysis, in whom HbA1c measurements have low reliability
- Practice point: A glucose management indicator derived from CGM data can be used to index glycaemia for individuals in whom HbA1c is not concordant with directly measured blood glucose levels or clinical symptoms
- Practice point: Daily glycaemic monitoring with CGM or SMBG may help prevent hypoglycaemia and improve glycaemic control when glucose-lowering therapies associated with risk of hypoglycaemia are used
- Practice point: For patients with T2D and CKD who choose not to do daily glycaemic monitoring by CGM or SMBG, glucose-lowering agents that pose a lower risk of hypoglycaemia are preferred and should be administered in doses that are appropriate for the level of eGF
- Practice point: CGM devices are rapidly evolving with multiple functionalities (e.g. real-time and intermittently scanned CGM). Newer CGM devices may offer advantages for certain patients, depending on their values, goals, and preferences.
Algorithm 5: Factors Guiding Decisions on Individual HbA1c Targets
- Recommendation, 1C: An individualised HbA1c target ranging from <6.5% to <8.0% in patients with diabetes and CKD not treated with dialysis is recommended (see Algorithm 5)
- Practice point: Safe achievement of lower HbA1c targets (e.g. <6.5% or <7.0%) may be facilitated by CGM or SMBG and by selection of antihyperglycaemic agents that are not associated with hypoglycaemia
- Practice point: CGM metrics, such as time in range and time in hypoglycaemia, may be considered as alternatives to HbA1c for defining glycaemic targets in some patients.
Lifestyle Interventions in Patients with Diabetes and CKD
- Practice point: Patients with diabetes and CKD should consume an individualised diet high in vegetables, fruits, whole grains, fibre, legumes, plant-based proteins, unsaturated fats, and nuts; and lower in processed meats, refined carbohydrates, and sweetened beverages
- Recommendation, 2C: Maintaining a protein intake of 0.8 g protein/kg (weight) per day for those with diabetes and CKD not treated with dialysis is suggested
- Practice point: Patients treated with haemodialysis, and particularly peritoneal dialysis, should consume between 1.0 and 1.2 g protein/kg (weight) per day
- Recommendation, 2C: Sodium intake of <2 g per day (or <90 mmol of sodium per day, or <5 g of sodium chloride per day) is suggested in patients with diabetes and CKD
- Practice point: Shared decision-making should be a cornerstone of patient-centred nutrition management in patients with diabetes and CKD
- Practice point: Accredited nutrition providers, registered dietitians and diabetes educators, community health workers, peer counsellors, or other health workers, should be engaged in the multidisciplinary nutrition care of patients with diabetes and CKD
- Practice point: Healthcare providers should consider cultural differences, food intolerances, variations in food resources, cooking skills, comorbidities, and cost when recommending dietary options to patients and their families.
- Recommendation, 1D: Patients with diabetes and CKD should be advised to undertake moderate-intensity physical activity for a cumulative duration of at least 150 minutes per week, or to a level compatible with their cardiovascular and physical tolerance
- Practice point: Recommendations for physical activity should consider age, ethnic background, presence of other comorbidities, and access to resources
- Practice point: Patients should be advised to avoid sedentary behaviour
- Practice point: For patients at higher risk of falls, healthcare providers should provide advice on the intensity of physical activity (low, moderate, or vigorous) and the type of exercises (aerobic versus resistance, or both)
- Practice point: Physicians should consider advising/encouraging patients with obesity, diabetes, and CKD to lose weight, particularly patients with eGFR ≥30 ml/min per 1.73 m2.
Glucose-lowering Therapies in Patients with Type 2 Diabetes and CKD
Algorithm 6: Selecting Glucose-lowering Drugs for Patients with T2D and CKD
- Practice point: Glycaemic management for patients with T2D and CKD should include lifestyle therapy, first-line treatment with metformin and a SGLT2i, and additional drug therapy as needed for glycaemic control (see Algorithm 6)
- Practice point: Most patients with T2D, CKD, and eGFR ≥30 ml/min per 1.73 m2 would benefit from treatment with both metformin and an SGLT2i
- Practice point: Patient preferences, comorbidities, eGFR, and cost should guide selection of additional drugs to manage glycaemia, when needed, with GLP-1 RA generally preferred.
- Recommendation, 1B: Treating patients with T2D, CKD, and an eGFR ≥30 ml/min per 1.73 m2 with metformin is recommended
- Practice point: Treat kidney transplant recipients with T2D and an eGFR ≥ 30 ml/min per 1.73 m2 with metformin according to recommendations for patients with T2D and CKD
- Practice point: Monitor eGFR in patients treated with metformin. Increase the frequency of monitoring when the eGFR is <60 ml/min per 1.73 m2 (see Algorithm 7)
- Practice point: Adjust the dose of metformin when the eGFR is <45 ml/min per 1.73 m2, and for some patients when the eGFR is 45–59 ml/min per 1.73 m2
- Practice point: Monitor patients for vitamin B12 deficiency when they are treated with metformin for more than 4 years.
Algorithm 7: Suggested Approach in Dosing Metformin Based on the Level of Kidney Function
Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RA)
- Recommendation, 1B: In patients with T2D and CKD who have not achieved individualised glycaemic targets despite use of metformin and SGLT2i, or who are unable to use those medications, a long-acting GLP-1 RA is recommended
- Practice point: The choice of GLP-1 RA should prioritise agents with documented cardiovascular benefits
- Practice point: To minimise gastrointestinal side effects, start with a low dose of GLP-1 RA, and titrate up slowly (see Table 1)
- Practice point: GLP-1 RA should not be used in combination with dipeptidyl peptidase-4 (DPP-4) inhibitors
- Practice point: The risk of hypoglycaemia is generally low with GLP-1 RA when used alone, but risk is increased when GLP-1 RA is used concomitantly with other medications such as sulfonylureas or insulin. The doses of sulfonylurea and/or insulin may need to be reduced
- Practice point: GLP-1 RA may be preferentially used in patients with obesity, T2D, and CKD to promote intentional weight loss.
Table 1: Dosing for Available GLP-1 RA and Dose Modification for CKD
|GLP-1 RA||Dose||CKD Adjustment|
|Dulaglutide||0.75 mg and 1.5 mg once weekly||No dosage adjustmentUse with eGFR >15 ml/min per 1.73 m2|
|Exenatide||10 mcg twice daily||Use with CrCl >30 ml/min|
|Exenatide extended-release||2 mg once weekly||Use with CrCl >30 ml/min|
|Liraglutide||0.6 mg, 1.2 mg, and 1.8 mg once daily||No dosage adjustment|
Limited data for severe CKD
|Lixisenatide||10 mcg and 20 mcg once daily||No dosage adjustment|
Limited data for severe CKD
|Semaglutide (injection)||0.5 mg and 1 mg once weekly||No dosage adjustment|
Limited data for severe CKD
|Semaglutide (oral)||3 mg, 7 mg, or 14 mg daily||No dosage adjustment|
Limited data for severe CKD
|© Kidney Disease: Improving Global Outcomes, 2022. Reproduced with permission. |
Abbreviations: CKD=chronic kidney disease; CrCl=creatinine clearance; eGFR=estimated glomerular filtration rate; GLP-1 RA=glucagon-like peptide-1 receptor agonist.
Approaches to Management of Patients with Diabetes and CKD
Self-Management Education Programmes
- Recommendation, 1C: The implementation of a structured self-management educational programme is recommended for care of people with diabetes and CKD
- Practice point: Healthcare systems should consider implementing a structured self-management programme for patients with diabetes and CKD, taking into consideration local context, cultures, and availability of resources.
Team-Based Integrated Care
- Recommendation, 2B: It is suggested that policymakers and institutional decision-makers implement team-based integrated care focused on risk evaluation and patient empowerment to provide comprehensive care in patients with diabetes and CKD
- Practice point: Team-based integrated care, supported by decision-makers, should be delivered by physicians and non-physician personnel (e.g. trained nurses and dieticians, pharmacists, healthcare assistants, community workers, and peer supporters) preferably with knowledge of CKD.