Is Diabetic kidney Disease treatable?

Diabetes With Kidney Disease

Patients with diabetic kidney disease are at a particularly high risk for a host of serious health issues, primarily due to cardiovascular complications and the progression of nephropathy. 

This progression often leads to the necessity for renal replacement therapy, a situation that is both physically and emotionally taxing for patients. 

Despite following traditional treatments like strict blood pressure and blood sugar control, using statins, and blocking the RAAS, these patients still face a significant residual risk.

The Advent of New Antidiabetic Medications

In recent years, the landscape of diabetes treatment has been transformed by introducing new classes of antidiabetic medications. 

SGLT2 inhibitors and GLP1 receptor activators are now effective treatments for reducing heart and kidney risks.

 These benefits extend beyond their effects on blood sugar levels, marking a significant shift in how diabetes is managed globally.

AHA's Review and Integrated Management Model

The American Heart Association (AHA) has reviewed the substantial pathophysiological and clinical evidence supporting the widespread use of these new medications. They propose an integrated management model involving a team of specialists to treat these patients effectively. 

This approach is crucial as patients with chronic kidney disease (CKD) and diabetes mellitus (DM) are at a notably high risk of cardiovascular events and the worsening of nephropathy, often culminating in the need for renal replacement therapy.

Residual Risk Despite Traditional Treatments

Even when blood glucose and blood pressure are well-controlled, and patients are on appropriate medications such as statins and RAAS blockers, the residual risk remains alarmingly high. 

However, a growing body of evidence supports the notion that new antidiabetic agents can significantly mitigate this risk. 

Both SGLT2 inhibitors and GLP1 receptor activators have shown promise in this regard. The AHA has systematically reviewed this evidence to establish its position on the matter.

Benefits of SGLT2 Inhibitors

SGLT2 inhibitors have demonstrated substantial cardiovascular benefits across multiple pivotal clinical trials. This has led the Food and Drug Administration (FDA) to approve these drugs for cardiovascular protection, independent of their effects on glycemic control. 

Research has indicated that these medications can decrease composite cardiovascular events by around 30%. Empagliflozin, in particular, is notable for significantly reducing cardiovascular mortality. 

Additionally, the DAPA-HF trial demonstrated that dapagliflozin offers benefits for heart failure patients, even those without diabetes.

In terms of renal benefits, SGLT2 inhibitors have consistently been shown to slow the decline in kidney function. The mechanisms behind these benefits are varied and still under investigation. 

However, the impact is clear: these drugs help preserve kidney function across a range of CKD stages. Trials like CREDENCE and DAPA-CKD have demonstrated the efficacy of these medications even in patients with moderate to severe CKD, including those without diabetes.

Subanalyses and Broader Implications

Subanalyses of these studies reveal that the cardiovascular and renal benefits of SGLT2 inhibitors are most pronounced in patients at higher risk. Nonetheless, these benefits are maintained across different levels of glomerular filtration and albuminuria and in both primary and secondary prevention contexts. 

As a result, guidelines have evolved to allow these drugs to be prescribed at various stages of CKD, reflecting their broad applicability. Importantly, the cardiorenal advantages of SGLT2 inhibitors are independent of both metabolic control and drug dosage. These treatments are generally safe, with major adverse events being infrequent, even among patients with CKD.

Benefits of GLP1 Receptor Activators

GLP1 receptor activators also offer significant cardioprotective benefits, particularly for patients with CKD. These drugs primarily reduce atherosclerotic cardiovascular events. They can be used until the advanced stages of CKD and have a notable impact on both glycemic control and weight management.

 However, the renal benefits of GLP1 receptor activators are more varied than those of SGLT2 inhibitors. Only liraglutide and subcutaneous semaglutide have shown positive trial results in reducing the progression to high-grade proteinuria rather than slowing the overall decline in kidney function.

 Despite this, their safety profile and cardioprotective effects make them an essential part of the treatment regimen for diabetic patients with CKD.

Despite the proven benefits of these new treatments, their adoption in routine clinical practice remains limited, especially among patients as well at the highest risk, such as those with nephropathy. 

This hesitancy may stem from the complexity of these treatments. To address this, the AHA committee suggests forming multidisciplinary teams that include cardiologists, nephrologists, endocrinologists, and primary care physicians.

Implementing a Multidisciplinary Approach

Implementing specific protocols that emphasize frequent screening and early diagnosis of CKD, along with a comprehensive assessment of cardiovascular risk, will enable healthcare providers to better identify patients who could benefit from SGLT2 inhibitors, GLP1 receptor activators, or both. 

This collaborative approach aims to enhance treatment safety, maximize patient adherence, and optimize the therapeutic benefits of these medications.

To explore further, SGLT2 inhibitors have consistently demonstrated their effectiveness in reducing cardiovascular events across numerous clinical trials. 

These drugs function by blocking the sodium-glucose cotransporter 2 in the kidneys, which increases glucose excretion through urine. This process not only aids in lowering blood sugar levels but also provides protective benefits for both the heart and kidneys.

 For instance, the EMPA-REG OUTCOME trial demonstrated that empagliflozin significantly reduced the risk of cardiovascular death, nonfatal heart attack, and nonfatal stroke. These findings have been echoed in subsequent studies, solidifying the role of SGLT2 inhibitors in cardiovascular risk reduction.

Renal Benefits of SGLT2 Inhibitors: Detailed Insights

On the renal front, SGLT2 inhibitors have shown promise in slowing the progression of kidney disease. The mechanisms are multifaceted, involving improved glycemic control, reduced blood pressure, and direct renal effects such as decreased hyperfiltration and reduced inflammation. 

For example, the CREDENCE trial revealed that canagliflozin lowered the risk of end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death in patients with type 2 diabetes and established nephropathy.

GLP1 receptor activators, conversely, mimic the incretin hormone GLP1, which boosts insulin secretion after meals. These medications also delay gastric emptying, curb appetite, and facilitate weight loss, offering notable advantages for individuals with type 2 diabetes. 

The cardiovascular benefits of this drug class have been underscored in trials like LEADER, where liraglutide demonstrated a reduction in major cardiovascular events, encompassing cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.

Renal Benefits of GLP1 Receptor Activators: Detailed Insights

In terms of renal outcomes, the benefits of GLP1 receptor activators have been more heterogeneous. While liraglutide and semaglutide have shown positive effects in reducing the progression to high-grade proteinuria, the overall impact on kidney function decline has been less clear compared to SGLT2 inhibitors. 

Nonetheless, their strong cardiovascular profile and additional benefits in glycemic control and weight management make GLP1 receptor activators a valuable option in the treatment arsenal for diabetic patients with CKD.

Incorporating these novel therapies into everyday clinical practice necessitates a fundamental shift in how diabetes and its associated complications are approached. The American Heart Association's endorsement of multidisciplinary teams marks a pivotal stride in this direction. 

Encouraging collaboration among diverse specialists enables healthcare providers to deliver comprehensive care that attends to both the cardiovascular and renal health needs of patients.

 Commencing early and consistent screenings for chronic kidney disease (CKD), alongside a thorough evaluation of cardiovascular risk factors, plays a crucial role in pinpointing individuals who are poised to gain substantial advantages from these pioneering treatments.

Conclusion

Ultimately, the objective is to elevate patient outcomes by harnessing the established advantages of SGLT2 inhibitors and GLP1 receptor activators. This strategy not only strives to alleviate the challenges posed by cardiovascular and renal complications.

 In diabetic individuals but also aims to enhance their overall quality of life. By adopting a holistic, patient-centered approach, the medical community can make significant strides in managing diabetic kidney disease and its associated risks.