Diabetic kidney disease and type 2 diabetes: best practice

CHRONIC kidney disease (CKD) is a common and potentially fatal condition that effects around 238 000 Australians. Type 2 diabetes is a leading cause of CKD worldwide. The prevalence of CKD in patients with type 2 diabetes is twice as high as in patients without type 2 diabetes.

As the occurrence of type 2 diabetes continues to increase both globally and within Australia, so does the incidence of diabetes-associated CKD, also known as diabetic kidney disease (DKD).

GPs play a fundamental role in identifying patients with type 2 diabetes who may have DKD and subsequently ensuring that they are treated with medications that have proven kidney protective effects. Access to new treatments with minimal side effects and high levels of tolerability will provide more options for GPs to manage the progression of DKD.

The current fundamental principles to delay the progression of DKD include tight metabolic and blood pressure control, and the use of renin-angiotensin system (RAS) blocking agents. However, many people with type 2 diabetes and DKD can still be affected with further decline in kidney function and increased risk of death, not only from kidney damage but also cardiovascular disease. Patients with type 2 diabetes are three times more likely to die from cardiovascular-related causes than from diabetes alone. Therefore, there is a high unmet need for early intervention to prevent kidney failure in people with type 2 diabetes.

All these factors point to an imminent need for early diagnosis, intervention, and disease-specific treatment options for patients with DKD. This article highlights methods to help early diagnosis of DKD as well as management strategies to reduce the risk of DKD progression after diagnosis.

Early diagnosis and screening

Early-stage DKD is usually a silent disease, with minimal clinical manifestations until the patient has progressed to an advanced stage of kidney disease, possibly to the point of requiring renal replacement therapy.

It is therefore crucial to proactively screen for markers of kidney disease in high-risk patients with type 2 diabetes for timely diagnosis. This includes:

• Blood tests, routine for patients with type 2 diabetes, are an easy way to measure estimated glomerular filtration rate (eGFR), a key marker for kidney function. A value of less than 60 mL/min/1.73m² indicates possible DKD.
• A spot urine sample can also be collected yearly in patients with type 2 diabetes to measure the albumin to creatinine ratio. A ratio greater than 2.5 mg/mmol in men or 3.5 mg/mmol in women is a potential marker of kidney damage.

It should be noted that a high albumin to creatinine ratio may also be indicator of cardiovascular disease.

Confirmed findings of an eGFR of less than 60 mL/min/1.73m² and/or the presence of albuminuria are required for the diagnosis and staging of CKD in patients with type 2 diabetes.

Extra consideration should be given to ruling out non-diabetic causes of CKD. Patients with rapidly increasing albuminuria or decreasing eGFR can be considered for referral to a nephrologist. Reaching an eGFR threshold of less than 30 mL/min/1.73m² can also be a nephrology referral trigger.

Pharmacological Intervention

Currently, the backbone of pharmacological interventions for DKD in patients living with type 2 diabetes involves the use of RAS blocking medications, as this system is usually upregulated in type 2 diabetes.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are also now recommended as a treatments for patients with DKD. This class of medication works by blocking glucose reabsorption within renal tubules. These inhibitors not only lower blood glucose levels by inducing glycosuria, but also act like diuretics and reduce blood pressure (possibly within the glomerulus) to protect against the progression of DKD.

For some time, there has been interest in using blockers of aldosterone action (promoted by RAS activation) to slow the progression of DKD. Aldosterone binds to the mineralocorticoid receptor and overactivation of this receptor is another key driver of DKD progression. However, the side effects and lack of tolerability of existing mineralocorticoid receptor antagonists are well recognised in clinical practice. Finerenone is the first-in-class non-steroidal mineralocorticoid receptor modulating option to be approved for DKD in type 2 diabetes in Australia (here and here). Recent major clinical trials have shown that the use of finerenone, in addition to normal standards of care, including RAS blocking agents, can significantly slow kidney disease progression, and reduce kidney-related deaths and cardiovascular events. In these trials the incidence of treatment-emergent adverse events was balanced between finerenone- and placebo-treated patients.

Finerenone is indicated by the Therapeutic Goods Administration to delay progressive decline of kidney function in adults with CKD associated with type 2 diabetes (with albuminuria), in addition to standard of care (the medication is not listed in the Pharmaceutical Benefits Scheme at present). Finerenone will be available as a once daily 10 mg or 20 mg tablet, with dosing based on eGFR and potassium thresholds. Finerenone is yet to be included within Australia’s clinical guidelines.

Lifestyle and metabolic management

In combination with pharmacological intervention, paying attention to lifestyle factors remains very advantageous for slowing down progression of kidney disease. These factors include maintaining a healthy weight, adherence to a regular exercise program, and restricting salt intake.

High blood pressure is a well known driver of chronic kidney disease, including DKD, and tight blood pressure control is the basis of preventing renal function decline in people with DKD. Kidney dysfunction is also a major risk factor for cardiovascular disease, so it is equally important to adopt aggressive management for cardiovascular risk factors, including maintaining lipid profile control through the use of statins. Studies have shown that maintaining good blood metabolic and pressure control can minimise the progression of DKD by up to 50%.

As the most frequent point of contact for patients with type 2 diabetes, GPs are well placed to develop meaningful relationships with patients, so are in the best position to help patients develop and maintain good risk factor management.

With the growing burden of DKD in patients with type 2 diabetes, GPs are uniquely placed to support high risk patients and identify early signs of kidney disease progression and to assist with risk factor modification. With major breakthroughs and advances in new kidney protective medications, GPs are better equipped than ever to prevent the progression of DKD and prolong a better quality of life for their patients.

Richard MacIsaac is Director of Endocrinology and Diabetes at St Vincent’s Hospital, Melbourne and a Professorial Fellow at the University of Melbourne. He is also a Senior Principal Research Associate at St Vincent’s Institute of Medical Research, an Honorary Clinical Research Fellow at the Bionics Institute of Australia and the Diabetic Kidney Disease co-stream leader for the Australian Centre for Accelerating Diabetes Innovations Research Centre (ACADI), University of Melbourne. He has published over 280 research articles.

The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the AMA, the MJA or InSight+ unless so stated.

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