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What Are The Early Predictive Indicators Of DKD?


Diabetic nephropathy (DKD) is a condition characterized by kidney damage resulting from long-term diabetes. Diabetes is a chronic disease that typically involves insufficient insulin production or abnormal utilization, leading to elevated blood sugar levels. High blood sugar levels can have adverse effects on various organs and systems, and one of these is the kidneys.

The progression of diabetic nephropathy is usually divided into three stages:

Increased glomerular filtration rate (GFR) stage: In the early stages of diabetes, the kidneys may exhibit an enhanced response to glucose filtration, leading to an increase in glomerular filtration rate.

Microalbuminuria stage: Over time, high blood sugar levels can induce structural changes in the glomeruli and renal tubules, causing the leakage of small amounts of albumin into the urine. This stage is known as microalbuminuria.

Clinical nephropathy stage: In the final stage of diabetic nephropathy, kidney function is impaired, and patients may experience symptoms such as proteinuria, hypertension, and edema. In extreme cases, dialysis or kidney transplantation may be necessary to replace kidney function.


Diagnosis Of DKD

Diabetic Kidney Disease (DKD) refers to chronic kidney disease (CKD) caused by diabetes, typically diagnosed clinically based on elevated urine albumin and/or a decline in estimated glomerular filtration rate (eGFR), while excluding other causes of CKD. The clinical characteristics of DKD include gradually progressing proteinuria, progressive decline in kidney function, and in the late stages, severe renal failure, making it one of the primary causes of death in diabetic patients.

Relying on a single screening indicator to assess kidney damage may have some limitations. Therefore, clinicians should combine various auxiliary examination methods to make a comprehensive judgment. Additionally, there should be an increased emphasis on recognizing and evaluating kidney damage in diabetic patients, standardizing the assessment of kidney damage in diabetic patients, and enhancing early prediction and diagnosis of DKD.

Laboratory Markers For Early Prediction And Diagnosis Of DKD

1.Significance of Early Prediction and Diagnosis of DKD

Early diagnosis of Diabetic Kidney Disease (DKD) is particularly crucial, as studies generally suggest that renal function damage is irreversible when eGFR (estimated glomerular filtration rate) falls below 30 mL·min-1·1.73 m-2. Initiating drug intervention early can delay the onset of organic kidney lesions. Timely detection of early glomerular, tubular, and interstitial kidney lesions is beneficial for the early diagnosis and treatment of DKD. A retrospective study involving 121,395 patients demonstrated that early diagnosis of DKD reduces the risk of progression to end-stage renal disease by 80%.

Diabetic patients should undergo timely assessments to identify potential kidney damage, allowing for early detection and intervention.

2.Biomarkers for Early Prediction of DKD

Urinary biomarkers in diabetic patients can provide insights into the affected areas of the kidneys, potential causes, and pathophysiological processes of DKD. In addition to eGFR (estimated glomerular filtration rate) and UACR (urine albumin-to-creatinine ratio), an increasing body of literature reports other laboratory testing indicators that can be used to assess DKD.

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3.Considerations for Urinary Biomarkers

Before analysis, attention should be paid to the sample collection time, containers, storage conditions and stability, other factors that may alter urinary protein levels (such as abdominal surgery, infections, high fever, high-protein diet), and specimen handling before testing.

During analysis, reliable screening of detection methods is essential, and quantification of urine albumin concentration is recommended. Immunoturbidimetry exhibits high sensitivity and specificity with a wide linear range, but requires specialized protein analyzers. Immunotransmission turbidimetry is simpler to operate but lacks the sensitivity and specificity of immunoturbidimetry. Additionally, appropriate methods for handling values beyond the detection range, calibration of creatinine, and routine urine examination should be chosen.

After analysis, due to the ongoing standardization work for urine component (especially protein) detection, variations in results may exist between different detection systems. Therefore, when evaluating changes in a patient’s urinary parameter over time, this aspect should be taken into consideration. It is recommended to use the same detection system when testing a specific urinary parameter for a patient.

Monitoring DKD

For patients with a disease duration of ≥5 years for type 1 diabetes, all type 2 diabetes patients, and all patients with hypertension, quantitative assessment of urinary albumin, eGFR, and other biomarkers reflecting damage to renal tubules and glomeruli (such as urine α1-MG, urine RBP, u-TF, urine IgG) should be performed at least annually. When these indicators are abnormal, the potential complications of CKD should be assessed and addressed.

The treatment of DKD is an integrated process, emphasizing etiological treatment and comprehensive prevention and treatment. While referring to treatment guidelines, attention should also be given to individualized treatment targets. The treatment strategy for DKD includes improving unhealthy lifestyles, nutritional adjustments, controlling proteinuria, and intensifying glycemic control. Additionally, controlling blood pressure, correcting lipid disorders, and improving traditional cardiovascular risk factors should be emphasized.

While widespread adoption of albuminuria screening and DKD assessment is common, focusing on the detection of tubular damage biomarkers aids in identifying earlier stages of DKD. Simultaneously, it holds significant clinical value in monitoring the progression of DKD, assessing the severity and prognosis of renal damage, and determining the effectiveness of therapeutic interventions.

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Treatment Approaches for Diabetic Kidney Disease

Comprehensive management is essential for patients with diabetic kidney disease. This includes adjustments to unhealthy lifestyles, control of risk factors (such as high blood sugar, hypertension, and lipid metabolism disorders), and diabetes education.

1. Lifestyle Modifications

  • Proper weight management.
  • Diabetes-specific diet.
  • Smoking cessation.
  • Regular physical activity.

2. Nutritional Management

For diabetic kidney disease patients not yet on dialysis, it is recommended to consume 0.8g of protein per kilogram of body weight daily. High-quality animal proteins are preferred as the primary source, and if necessary, supplementation with ketoacid analogs may be considered.

3. Blood Sugar Control

It is recommended for all diabetic kidney disease patients to undergo appropriate glycemic control.

SGLT-2 Inhibitors: Research has shown that SGLT-2 inhibitors have renal protective effects in addition to glycemic control. For T2DM patients with diabetic kidney disease, it is recommended to use SGLT2 inhibitors in patients with an eGFR ≥ 45 ml/min/1.73m^2 to reduce the risk of diabetic kidney disease progression and/or cardiovascular events.

GLP-1 Receptor Agonists: Research has indicated that GLP-1RA can reduce the risk of significant albuminuria in diabetic patients. It can be considered for patients with an eGFR ≥ 30 ml/min/1.73m^2.

LUCIFINE Finerenone Tablets:LUCIFINE Finerenone Tablets Is a non-steroidal mineralocorticoid receptor antagonist (MRA) indicated to reduce the risk of sustained eGFR decline end stage kidney disease, cardiovascular death non-fatal myocardial infarction, and hospitalization for hear failure in adult patients with chronic kidney disease(CKD) associated with type 2 diabetes T2D).

LUCIFINE finerenone tablets
LUCIFINE finerenone tablets

For patients with impaired kidney function, it is advisable to prioritize the use of antidiabetic medications with lower renal excretion. Severe kidney function impairment may warrant insulin therapy.

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