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Diabetic kidney disease, how much do you know?

Diabetic nephropathy, how much do you know

Diabetic kidney disease is one of the most severe complications of diabetes, accounting for one-third of primary causes of kidney failure. The incidence of diabetic kidney disease is on the rise, and it has become the second leading cause of end-stage kidney disease, second only to various forms of glomerulonephritis. Among the complications of type 2 diabetes, it ranks second only to cardiovascular diseases. In the mid-term clinical presentation, it is characterized by the presence of a large amount of protein in the urine, indicated by foamy urine. Other symptoms may include swelling, high blood pressure, low blood protein levels, and reduced kidney function. If the condition is not controlled in a timely manner, it can progress to uremia, which is a major cause of death in type 1 diabetes patients. However, there is still a lack of awareness about diabetic kidney disease, and many people have a blind spot when it comes to this condition. People with diabetes need to be vigilant and educate themselves to prevent the occurrence of complications.

Due to its complex metabolic disturbances, once it progresses to end-stage kidney disease, it is often more challenging to treat than other kidney diseases. Therefore, timely prevention and management are of significant importance in delaying the progression of diabetic kidney disease.

The causes of diabetic kidney disease include

1. Abnormal glucose metabolism

High blood glucose levels and increased production of advanced glycation end products (AGEs) can lead to the proliferation of mesangial cells, increased extracellular matrix, mesangial expansion, and thickening of the glomerular basement membrane. Poor blood sugar control in diabetic patients can accelerate the onset and progression of diabetic kidney disease, while good blood sugar control can significantly delay its development.

2. Renal hemodynamic changes

Early in diabetic kidney disease, abnormal renal hemodynamics can be observed, characterized by high glomerular perfusion and filtration. Renal blood flow and glomerular filtration rate increase, and this increase is more significant after the intake of protein.

3. High blood pressure

Although high blood pressure is not directly related to the onset of diabetic kidney disease, pre-existing hypertension or an increase in blood pressure during the course of the disease, especially during the period of microalbuminuria, can accelerate the progression of diabetic kidney disease and worsen kidney function, leading to increased excretion of urinary albumin.

Other contributing factors may include abnormalities in the metabolism of vasoactive substances, genetic factors, and the duration of the disease.

Development of diabetic kidney disease

According to the development of diabetic nephropathy, it can be divided into five stages from mild to severe (the treatment of diabetes also varies according to different stages).

Stage 1: Hyperfiltration and Kidney Enlargement Phase

This early change is consistent with high blood glucose levels and can return to normal after strict blood sugar control and insulin therapy for several weeks to months.

Treatment focus:

Maintain good lifestyle habits and control factors that contribute to atherosclerosis, such as high blood sugar, high blood pressure, high blood lipids, high uric acid, high blood viscosity, overweight, and smoking.

For diabetic patients with normal kidney function, the daily protein intake should be 0.8 grams per kilogram of body weight.

When choosing medications to lower blood pressure, blood lipids, and blood sugar, consider their impact on kidney function and adjust them according to the stage of kidney function impairment.

Diabetic nephropathy, how much do you know

Stage 2: Intermittent Microalbuminuria Phase

Both of these stages share common characteristics of kidney enlargement and increased glomerular filtration rate. However, patients do not exhibit clinical symptoms, kidney function remains normal, and there is no urinary protein excretion. The only difference is that in the second stage of diabetic kidney disease, patients do not show an increase in urinary albumin excretion at rest, but albumin excretion increases after exercise. Additionally, there are mild abnormalities in the microscopic tissue structure of the kidneys. With good blood sugar control during this stage, patients can remain stable in this phase for an extended period.

Treatment focus:

Continue to maintain lifestyle interventions.

After a decrease in glomerular filtration rate, the daily protein intake should be in the range of 0.6 to 0.8 grams per kilogram of body weight.

Antidiabetic medications: Avoid the use of sulfonylurea antidiabetic drugs such as glyburide and glimepiride as much as possible and actively use insulin for blood sugar control.

Stage 3: Early Diabetic Kidney Disease Phase

Characterized by persistent microalbuminuria, with 24-hour urine protein levels ranging from 30 to 300 milligrams.

Treatment focus:

Low-protein diet, blood sugar control, blood pressure management, and lipid regulation. Pay attention to factors that can harm the kidneys, such as infections, high uric acid levels, urinary tract obstruction due to stones, kidney swelling, and kidney-toxic medications.

Initiate insulin therapy early to lower blood sugar, avoiding the use of medications that are harmful to the kidneys.

Control high blood pressure, maintaining the target blood pressure of ≤130/80 mmHg (≤140/80 mmHg for elderly patients). The preferred medications are renin-angiotensin system inhibitors (ACEIs or ARBs) as they can reduce urinary albumin. Since these medications may lead to a temporary decrease in glomerular filtration rate, it’s important to monitor blood creatinine and potassium levels in the first 1-2 weeks of using these drugs.

Stage 4: Clinical Diabetic Kidney Disease Phase

This stage is characterized by significant proteinuria, with 24-hour urine protein levels exceeding 500 milligrams. Urinary creatinine levels increase significantly, and there may be accompanying symptoms such as edema and high blood pressure.

Treatment focus:

Aggressively control blood sugar. In the dietary management of diabetes, the primary protein source should be high-quality animal protein. Daily protein intake should be ≤0.6 grams per kilogram of body weight, and it may be necessary to supplement with complex alpha-ketoacid analogs.

Patients with impaired kidney function should choose antidiabetic medications that are excreted less through the kidneys. For patients with severe kidney dysfunction, insulin therapy is preferred, with short-acting insulin to reduce the risk of hypoglycemia. When blood creatinine levels are greater than 132.6 μmol/L for males, 123.8 μmol/L for females, or GFR is less than 45 ml/min, metformin-type drugs should be avoided.

Use antiplatelet aggregation and adhesion medications such as aspirin, clopidogrel, pentoxifylline, or heparin. Consider using calcium dobesilate, which can help improve diabetic microvascular complications, especially in controlling blood sugar and microvascular improvements.

Continue strict control of blood pressure and blood lipids, selecting the appropriate medications.

Stage 5: Kidney Failure Phase

Proteinuria, edema, high blood pressure worsen further, and complications such as anemia, electrolyte imbalances, acidosis, nausea, vomiting, and renal osteodystrophy may appear. This stage represents uremia, and it necessitates either kidney dialysis or kidney transplantation.

Treatment focus:

Follow a low-salt, low-protein, low-fat diet, and limit fluid intake as appropriate. Daily protein intake should be ≤0.6 grams per kilogram of body weight, and complex alpha-ketoacid analogs may need to be supplemented.

Treat various complications through specialized medical care.

Dialysis and transplantation:

These interventions are recommended when glomerular filtration rate falls below 15 ml/min or when there are challenging conditions such as heart failure, severe gastrointestinal symptoms, and uncontrolled hypertension. The timing for dialysis initiation should be slightly earlier than for non-diabetic kidney disease patients. Generally, when blood creatinine levels reach 530-710 μmol/L and creatinine clearance is 10-15 ml/min, dialysis should be considered.

For diabetic kidney disease patients, the key to kidney protection lies in early prevention. It’s crucial to proactively adjust your blood sugar management plan, closely monitor blood sugar levels, and rigorously control your blood sugar. In clinical practice, patients with existing kidney damage due to diabetes are encouraged to initiate intensive insulin therapy as early as possible, aiming to maintain stable blood sugar levels within a healthy range (HbA1c < 7%). Research has shown that strict blood sugar control can reduce the risk of developing microalbuminuria by one-third. For those already experiencing microalbuminuria, it can reduce the risk of progressing to significant proteinuria by half.

Improving your lifestyle can also help control blood sugar. Firstly, maintaining a regular daily routine, getting enough rest, and engaging in regular exercise can benefit glucose metabolism. Secondly, regular self-monitoring of blood sugar is an essential tool for blood sugar control.

New medicine for treating diabetic nephropathy – 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)

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of a drug and may not reflect the rates observed in practice.

The safety of LUCIFINE was evaluated in 2 randomized, double-blind, placebo-controlled, multicenter pivotal phase 3 studies, FIDELIO-DKD and FIGARO-DKDin which a total of 6510 patients were treated with 10 or 20 mg once daily over a mean duration of 2.2 and 2.9 years, respectively.

Overall, serious adverse events occurred in 32% of patients receiving LUCIFINE and in 34% of patients receiving placebo in the FIDELIO-DKD study: the findings were similar in the FIGARODKD study. Permanent discontinuations due to adverse events also occurred in a similar proportion of patients in the two studies (6-7% of patients receiving LUCIFINE and in 5-6% of patients receiving placebo).

The most frequently reported (≥10%)adverse reaction in both studies was hyperkalemia [see Warnings and Precautions(5.1)]. Hospitalization due to Hyperkalemia for the LUCIFINE was 0.9% vs 0.2% in the placebo group across both studies. Hyperkalemia led to permanent discontinuation of treatment in 1.7% receiving LUCIFINE versus 0.6% of patients receiving placebo across both studies.

LUCIFINE is a CYP3A4 substrate. Concomitant use with a strong CYP3A4 inhibitor increases Finerenone exposure, which may increase the risk of LUCIFINE adverse reactions. Concomitant Use of LUCIFINE with strong CYP3A4 inhibitors is contraindicated see Contraindications (4) Avoid concomitant intake of grapefruit or grapefruit juice.

Moderate and Weak CYP3A4 Inhibitors LUCIFINE is a CYP3A4 substrate. Concomitant use with a moderate or weak CYP3A4 inhibitor increases Finerenone exposure, which may increase the risk of LUCIFINE adverse reactions. Monitor serum potassium during drug initiation or dosage adjustment of either LUCIFINE or the moderate or weak CYP3A4 inhibitor, and adjust LUCIFINE dosage as appropriate [(see Dosing and Administration (2.3) and Drug interaction (7 .2)]. Strong and Moderate CYP3A4 inducers.

LUCIFINE is a CYP3A4 substrate. Concomitant use of LUCIFINE with a strong or moderate CYP3A4 inducer decreases Finerenone exposure. which may reduce the efficacy of LUCIFINE. Avoid concomitant use of LUCIFINE with strong or moderate CYP3A4 inducers.

LUCIFINE-Finerenone-Tablets
LUCIFINE Finerenone Tablets

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