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Insulin Insulin therapy in CKD patients in stages 1 to 3A is no different from patients without CKD . However , once stage 3B ( eGFR 30-44mL / min / 1.73m 2 ) is reached , insulin requirements may be lower because insulin clearance is lower , and the risk of hypoglycaemia is higher .
Pharmacological approaches with benefit in type 2 diabetes and chronic kidney disease
For many years renin-angiotensin system ( RAS )
blockade has formed the basis of management of diabetes-associated CKD . RAS blockade reduces proteinuria and slows eGFR decline . 12 The emergence of the SGLT2i has changed the landscape of management of proteinuric kidney disease . While imparting a modest hypoglycaemic effect , the cardio- and reno-protective effects of SGLT2i are profound , resulting in their rapid integration into guidelines .
SGLT2i are currently recommended for people with proteinuric kidney disease ( irrespective of T2DM status ) with an eGFR 25-75mL / min / 1.73m 2 and a urine albumin-creatinine ratio ( uACR ) 22.6-565mg / mmol . SGLT2i are generally well tolerated although an excess of genital mycotic infections has been reported . The risk of euglycaemic ketoacidosis is increased twofold in the presence of T2DM , but is rare in the absence of T2DM . 13 Euglycaemic ketoacidosis is most likely to occur when there is concomitant insulinopenia and dehydration . 14 , 15 This highlights two important considerations when prescribing SGLT2i . The first is to ensure that diabetes is truly T2DM and not latent autoimmune diabetes in adults ( LADA ), which is associated with absolute
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insulin deficiency and represents approximately 10 % of people thought to have T2DM . 16 Currently SGLT2i are contraindicated in people with insulin deficiency ( such as T1DM and LADA ). The second is to ensure that a sick day management plan is in place which outlines , in the setting of intercurrent illness , when medications should be withheld , which medications should be withheld and when they should be recommenced . Kidney Health Australia has a sick day management plan template available for use via the health professionals hub ( see online resources ).
Non-steroidal mineralocorticoid receptor antagonists ( nsMRA ) are PBS-listed for use in Australia with the following indication : diagnosis of CKD with T2DM ; eGFR ≥ 25mL / min / 1.73m 2 ; uACR ≥ 22.6mg / mmol on top of RAS blockade and SGLT2i .
Treatment targets
To reduce morbidity and mortality for patients
with diabetes and CKD it is recommended to aim for waist circumference < 94cm in men and < 80cm in women ; BP < 130 / 80mmHg and reduction in uACR of 30 %. HbA1c targets should be individualised ( see figure 2 ), however , with the knowledge that a strong and linear cross-sectional association between the HbA1c and CKD and cardiovascular disease ( CVD ) exists . An increase in HbA1c levels of 1 % was associated with a 30-40 % increase in CKD or CVD , evident from HbA1c of 5.5 %. 17
Chronic kidney diseaseassociated risks
Diabetes associated CKD confers significant
risk of progressive kidney disease and CVD . The risk of kidney failure can be predicted
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using the Kidney Failure Risk Equation ( see online resources ), which has been validated in an Australian population . 19
The presence of moderate to severe CKD , defined as an eGFR < 45mL / min / 1.73m 2 and uACR > 30mg / mmol , heralds very high CVD risk . While updated guidelines to CVD risk calculation are available ( see online resources ), they should not be used in someone who is already at high risk based on the severity of CKD-alone , and attention should be directed to addressing CVD risk factors in these patients . In addition to the targets outlined above , current international guidelines suggest that a single lipid measurement be performed and treatment with a statin or statin / ezetimibe commenced without reference to an LDL threshold or target . 20 For those on dialysis , pharmacological therapy is not advised . Kidney Disease Improving Global Outcomes guidelines recommend that hypertriglyceridaemia should be managed with lifestyle advice with potential benefits of fibric acid derivatives ( lower CVD events and death ) outweighed by the harms ( hospitalisation and worsening kidney function ). 21 Aspirin is not routinely recommended for the primary prevention of CVD in people with CKD as there is no evidence of benefit . 22
Conclusion
CKD arising in the presence of diabetes is often due to diabetes . ' Unusual ' features should alert the clinician to potential alternative coexisting pathologies . Lifestyle measures are foundational in the management of T2DM-associated CKD , and reducing carbohydrate intake particularly at breakfast is a small change that can improve glycaemic control . In addition , using hypoglycaemic
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medications with cardiorenoprotective effects and minimising doses of obesogenic drugs such as insulin and the sulfonylureas can be beneficial . Together with the therapeutic backbone of RAS blockade , SGLT2i and nsMRA , preservation of kidney function is possible with associated reductions in morbidity and mortality .
The diagnosis of CKD can be overwhelming . For those living with kidney disease and their carers , Kidney Health Australia provides several programs and services that can offer tailored advice , resources , and peer connection . Call the Kidney Helpline on 1800 454 363 or visit the Kidney Health Australia website ( see online resources ) to find out more . For health professionals , the CKD Management in Primary Care Handbook is available either as a hard copy or free download ; resources , professional development and registration for upcoming webinars are all available on the Kidney Health Professional Hub ( see online resources ).
References on request from kate . kelso @ adg . com . au
Online resources
• Kidney Health Australia kidney . org . au
• Kidney Health Australia — Kidney Health Professional Hub , including sick day management resources kidney . org . au / HPHub
• Kidney Failure Risk Equation kidneyfailurerisk . com
• Australian CVD Risk Calculator cvdcheck . org . au
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< 6.5 % |
HbA1c |
< 8.0 % |
|
CKD G1 ( eGFR ≥90 ) |
Severity of CKD |
CKD G5 ( eGFR < 15 ) |
|
Absent / minor |
Macrovascular complications |
Present / severe |
|
Few |
Comorbidities |
Many |
|
Long |
Life expectancy |
Short |
|
Present |
Hypoglycaemia awareness |
Impaired |
|
Available |
Resources for hypoglycaemia management |
Scarce |
|
Low |
Propensity of treatment to cause hypoglycaemia |
High |
|