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Job Code: PC-GB-102832                         Date of preparation: March 2021



This promotional module has been initiated, funded and reviewed by Boehringer Ingelheim. The content of this industry-supported learning activity has been generated by Practice Nurse.

INTRODUCTION

Renal impairment frequently co-exists with diabetes.1 As many agents used to control blood glucose are metabolised by the kidneys, reduced renal function has important implications for the choice and dose of oral hypoglycaemic agents.

This module aims to raise awareness of how chronic kidney disease impacts on the management of hyperglycaemia, including the need for dose reduction for many agents used in the management of type 2 diabetes.

LEARNING OBJECTIVES

On completion of this module, the general practice nurse should:

  • Be familiar with the risk of declining renal function over time in patients with type 2 diabetes
  • Be able to identify the factors that lead to the development of diabetic kidney disease
  • Understand how to diagnose renal impairment and stage CKD
  • Be aware of how CKD impacts on the management of hyperglycaemia, including the need for dose reduction for many agents used in the management of type 2 diabetes

This module is one of a series of five. Others in the series are:

This resource is provided at an intermediate level. Read the article and answer the self-assessment questions, and reflect on what you have learned.

Complete the resource to obtain a certificate to include in your revalidation portfolio. You should record the time spent on this resource in your CPD log.

Renal considerations in patients with type 2 diabetes

Type 2 diabetes and renal function

Diabetic kidney disease (DKD*), also known as diabetic nephropathy, is the leading cause of chronic kidney disease (CKD) in the UK.2 It affects people with both type 1 and type 2 diabetes.2 Renal function may decline over time, and without appropriate intervention, can lead to end-stage renal disease (ESRD).3 More than 10,000 people in the UK have ESRD resulting from their diabetes, and people with diabetes are five times more likely to need renal replacement therapy (RRT).3 These patients, especially those with type 2 diabetes, are at significant cardiovascular risk.2

The pathological changes of diabetic kidney disease result from a combination of hyperglycaemia, dyslipidaemia and hypertension – both systemic hypertension and raised arterial pressure within the kidney itself (glomerular hypertension).4

These factors are also known to increase cardiovascular risk and indeed other aspects of cardiovascular disease (CVD) pathophysiology are thought to influence the development of DKD.5 This means that when someone with diabetes is diagnosed with CKD, the aim should be to delay progression and improve both renal and cardiovascular outcomes.

If recognised early, DKD in patients with type 2 diabetes can be treated: tight control of both blood glucose levels and blood pressure significantly reduces progression of DKD. Treatment of DKD reduces cardiovascular complications as well as kidney failure.6

*Diabetic kidney disease (DKD) or diabetic nephropathy refers to CKD caused by diabetes

Diagnosing CKD and DKD

The diagnosis of renal impairment is made on the basis of abnormal blood and/or urine tests. A blood test is used to estimate glomerular filtration rate (eGFR) and this, along with a urine test that measures the albumin creatinine ratio (ACR) can help to identify people with or at risk of chronic kidney disease (CKD).

Care should be taken to repeat abnormal tests in order to ensure that any change is sustained and not transitory, and to identify the presence of acute kidney injury (AKI), which will require more urgent intervention. Thus it is important that an abnormal eGFR is recorded at least three times over a period of 90 days to confirm the diagnosis of renal impairment and rate of progression. If a reduced eGFR (less than 60ml/min/1.73m²) has been recorded for the first time, a repeat test should be carried out within 2 weeks to exclude AKI.1

The risk of adverse outcomes increases with increasing ACR and decreasing GFR (Figure 1).1

Adapted from NICE CG182.1

The impact of renal impairment on managing blood glucose

As of December 2020, NICE is to update its guideline on the management of type 2 diabetes,7 but currently recommends the use of metformin* first line, followed by the addition of a second agent if blood glucose levels rise to 58 mmol/mol (first intensification).8

However, evidence from key cardiovascular outcome trials (CVOTs) suggests that the clinical characteristics of the individual patient should be used to inform the choice of medication at first intensification.7 These include the presence of established CVD, or comorbidities such as heart failure or chronic kidney disease, or older age and frailty. NICE therefore proposes to update its medication pathway to focus on CVD, renal disease, and other relevant clinical characteristics.7

NICE’s current guideline recommends the addition of a DPP-4 inhibitor, pioglitazone (exercise particular caution if the patient is at high risk of the adverse events of the drug – refer to the Summary of Product Characteristics [SmPC] for further details), a sulfonylurea or SGLT2 inhibitor at first intensification.8

If a combination of two drugs does not achieve adequate blood glucose control then a third agent should be added (second intensification).8

*In patients with type 2 diabetes and impaired renal function, the dose of metformin may need to be adjusted. It should be reviewed if the eGFR falls below 45/ml/minute/1.73m2, and metformin should be discontinued if eGFR is below 30/ml/minute/1.73m2.8,9 Dose adjustment or avoidance is also required for sulfonylureas.9

In patients with reduced renal function and type 2 diabetes, a DPP-4 inhibitor that does not require dose adjustment at any level of renal impairment, (e.g. linagliptin [Trajenta®]) would be appropriate.10 Linagliptin is also the only DPP-4 inhibitor to have its renal safety profile confirmed (as a pre-specified secondary outcome) in the CARMELINA cardiovascular outcome trial (CVOT), in which 74% of patients had pre-existing CKD.11

Renal impairment will have a significant impact on the choice of hypoglycaemic agent, so it is important to check for warnings in the SmPC for each drug before prescribing.

Renal impairment and the risk of cardiovascular disease (CVD)

Hypertension can worsen CKD and vice versa so it is important to treat blood pressure effectively. Angiotensin converting enzyme (ACE) inhibitors are known to have a positive effect on the kidneys and offer renoprotection so these are often the first choice therapy when treating people who have hypertension, diabetes and CKD.12

NICE CKD guidelines1 state that unless contraindicated, an ACE inhibitor or an angiotensin receptor blocker (ARB) should be offered to all people with CKD and diabetes who have an ACR of 3 mg/mmol or more (ACR category A2 or A3) and/or those who have hypertension and an ACR of 30 mg/mmol or more (ACR category A3).

The dose of medication may need to be adjusted (up or down) depending on the stage of CKD and/or HbA1c.

However, many people will need more than one antihypertensive drug to get their blood pressure to target so the combination of an ACE inhibitor or ARB (A) with a calcium channel blocker (C) or thiazide-like diuretic (D) should be added to get the patient to target (130/80mmHg in people with diabetes and kidney disease). The usual approach is A + C then D.13

Lifestyle interventions are always the key to reducing CVD risk, both in the general population as well as those people who have diabetes, so advice and support should be offered on the benefits of weight management, healthy eating, an active lifestyle and avoiding smoking.

Conclusion

People with diabetes are at increased risk of CKD when compared with the general population. The combination of diabetes, hypertension and CKD increases the potential for people to develop CVD and/or end stage renal disease. Blood pressure control using angiotensin blocking agents (ACE inhibitors and ARBs) and other blood pressure and lipid lowering therapies as required will help to protect people with diabetes from both of these complications. Lifestyle interventions will offer additional benefit and improve risk reduction. In people with CKD, care should be taken when initiating, intensifying or adjusting medication, specifically those used to reduce blood glucose levels as licenses vary even within drug classes.

In the self-assessment that follows, hypothetical case scenarios based on fictitious patients with type 2 diabetes are presented. Please refer to the relevant Summary of Product Characteristics before prescribing any of the medications mentioned.  

Please note that neither Practice Nurse nor Boehringer Ingelheim have any control over the content of the external websites listed in the references below.

References

1. NICE CG182. Chronic kidney disease in adults: assessment and management, 2014 (updated 2015). https://www.nice.org.uk/Guidance/cg182 [Accessed March 2021]

2. Min TZ, Stephens MW, Kumar P, Chudleigh RA. Renal complications of diabetes. British Medical Bulletin 2012;104:113-127

3. Diabetes UK. Us, diabetes and a lot of facts and stats. https://www.diabetes.org.uk/professionals/position-statements-reports/statistics [Accessed March 2021]

4. Marshall SM. Natural history and clinical characteristics of CKD in type 1 and type 2 diabetes mellitus. Adv Chronic Kidney Dis 2014;21(3):267-72.

5. Cheng H, Harris RC. Renal endothelial dysfunction in diabetic nephropathy. Cardiovasc Hematol Disord Drug Targets 2014;14(1):22-33.

6. Diabetes UK. Preventing kidney failure in people with diabetes: Position statement; August 2016. https://www.diabetes.org.uk/professionals/position-statements-reports/specialist-care-for-children-and-adults-and-complications/preventing-kidney-failure-in-people-with-diabetes [Accessed March 2021]

7. NICE. 2019 surveillance of diabetes (NICE guidelines NG17,NG18, NG19 and NG28). https://www.nice.org.uk/guidance/ng28/resources/2019-surveillance-of-diabetes-nice-guidelines-ng17-ng18-ng19-and-ng28-6837997933/chapter/Surveillance-decision?tab=evidence [Accessed March 2021]

8. NICE NG28. Type 2 diabetes in adults: management, 2015 (updated 2016) https://www.nice.org.uk/guidance/ng28 [Accessed March 2021]

9. Davies MJ, D’Alessio DA, Fradkin F, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018;41:2669-2701

10. Trajenta (linagliptin) Summary of Product Characteristics, Boehringer Ingelheim Ltd, 2019. https://www.medicines.org.uk/emc/medicine/25000 

11. Rosenstock J, Perkovic V, Johansen OE, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk. JAMA 2019;321(1):69-79

12. HOPE Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet 2000;355: 253-59.

13. NICE CG127. Hypertension in adults: diagnosis and management, 2011. https://www.nice.org.uk/guidance/cg127 [Accessed March 2021]

14. Strain WD, Hope SV, Green A, et al. Type 2 diabetes mellitus in older people: a brief statement of key principles of modern day management including the assessment of frailty. A national collaborative stakeholder initiative. Diabetic Medicine 2018; 35(7):838-245

15. Griffin K, Bidani A. Potential risks of calcium channel blockers in chronic kidney disease. Curr Cardiol Rep 2008;10:448-55


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