Recent advents in the arena of diabetic kidney disease

Avani Dave, Jai Hind College

What is DKD?

Diabetes is the major cause of chronic kidney disease (CKD) in the United States and across the world. Globally, an estimated 422 million individuals have diabetes, with up to 40% of them developing CKD over their lifespan. Diabetic kidney disease (DKD) is a pathological phenotype that does not have a particular pathological phenotype. In individuals with diabetes, it can be diagnosed clinically based on the presence of chronic albuminuria and/or a prolonged decrease in the estimated glomerular filtration rate (eGFR). DKD is generally discovered five years after a type 1 diabetes diagnosis, although it can also be detected almost immediately at the time of a type 2 diabetes diagnosis. 

Despite the fact that a kidney biopsy can confirm the diagnosis of DKD, it is generally explored when another disease is suspected. Albuminuria is now divided into two categories: mild (30 to 300 mg/g) and severe (> 300 mg/g). Nonetheless, among individuals with diabetes, any degree of albuminuria has been linked to an elevated risk of CKD development, end-stage kidney disease (ESKD), poor cardiovascular disease outcomes, and death. 

In diabetic patients without albuminuria, a decreased eGFR has been found; nevertheless, the course of DKD appears to be delayed in these individuals. Furthermore, in patients with diabetes, the coexistence of albuminuria with a decreased eGFR raises the risk of cardiovascular events and death. 

What causes DKD?

The primary metabolic anomalies that impact the kidneys and are linked with inflammation and finally fibrosis in diabetic patients include:

• Hyperaminoacidemia
• Glomerular hyperfiltration
• Hyperperfusion
• Hyperglycemia. 

The traditional natural history of DKD is defined by glomerular hyperfiltration moving to albuminuria, and subsequently a decrease in kidney function. 

• An enhanced proximal tubular reabsorption of glucose via sodium-glucose cotransporter 2 leads to a reduction in tubuloglomerular feedback, according to one mechanistic theory. The afferent arteriole dilates, and glomerular perfusion increases as a result of this. 
• Increased angiotensin II production, on the other hand, results in efferent arteriole vasoconstriction. The end result is an increase in intraglomerular pressure, which results in glomerular hyperfiltration. 
• Furthermore, glomerular enlargement might be a result of systemic hypertension or obesity, which can lead to glomerular hyperfiltration.

A variety of additional variables may play a role in the development of DKD. For instance, 

• Oxidative stress is one of them. The synthesis of many cytokines is induced by the activation of advanced glycation end-products (AGE) receptors, which are found on multiple cell types in the kidneys. Hyperglycemia increases AGE synthesis. 
• Endothelial instability enhanced vascular proliferation, renal hypertrophy, podocyte damage, tubular epithelial cell injury, and increased cytokine production are the overall effects of these various pathways.
• The thickening of the glomerular basement membrane is the first structural alteration in DKD, followed by mesangial matrix enlargement and foot process effacement. DKD progression is marked by segmental mesangiolysis and Kimmelstiel–Wilson nodules. 

Treatment options: 

In the early stages of DKD, strict glycemic management is essential for preventing the illness. Intensive glucose management, on the other hand, has not been demonstrated to lower the risk of CKD progression or cardiovascular mortality in later stages of DKD in a number of trials. 

The Kidney Disease: Improving Global Outcomes (KDIGO) recommendations suggest an HbA1c goal of 6.5 to 8.0%, with the exact target determined by the severity of hypoglycemia risk in each patient.

For individuals with DKD with GFR > 30 ml/min per 1.73 m2, current guidelines recommend taking both metformin and sodium-glucose cotransporter 2 inhibitors for glycemic management. If needed, glucagon-like peptide-1 receptor agonists can be used to treat hyperglycemia.

In all patients with CKD with albuminuria, regardless of their diabetes status, the KDIGO recommendations advocate taking an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) to keep blood pressure below 130/80 mmHg. 

In terms of non-pharmacological therapies, the KDIGO guidelines recommend that DKD patients follow a low sodium diet (less than 2 g/day), maintain a protein intake of 0.8 g/kg/day for patients who are not on dialysis, and engage in moderate-intensity physical activity for at least 150 minutes per week as tolerated.

Better diagnostic techniques and highly efficacious treatment plans are desired to be able to combat the adversities linked to DKD. 

Also read: Is tryptophan deficiency associated with inflammation?

References: Hanouneh, M., Echouffo Tcheugui, J. B., & Jaar, B. G. (2021). Recent advances in diabetic kidney disease. BMC Medicine, 19(1), 180. https://doi.org/10.1186/s12916-021-02050-0

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Author’s Info: Avani Dave is currently in the final year of her bachelor’s degree, majoring in Life Sciences. Holding a good academic and extra-curricular record, she is on a constant journey of acquiring exposure in her field of interest while simultaneously not limiting herself to just that. Avani likes studying Diseases and Syndromes and everything under this umbrella! That being said, she is adept at working across departments and promises to deliver.