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Factors that Accelerate the Progression of Diabetic Kidney Disease

diabetic kidney disease

What is Diabetic Kidney Disease?

The definition of Diabetic Kidney Disease (DKD) is the presence of albuminuria (defined as an increase in urinary albumin excretion ≥3.4 mg/mmol [30 mg/g]), progressive decline in estimated glomerular filtration rate (eGFR) estimated during the long-term course of diabetes (appearing after more than 10 years in type 1 diabetes; possibly present at the time of diagnosis in type 2 diabetes), and typically accompanied by retinopathy. In most diabetic patients, if these characteristics are met, chronic kidney disease (CKD) caused by diabetes may be considered.

The main symptoms of diabetic kidney disease (DKD)

Diabetic kidney damage may already exist in the early stages of diabetes, but there are often no clinical manifestations initially. Symptoms typically manifest more than 10 years after the onset of the disease. Initially, there is an increase in urinary protein, often accompanied by casts, microscopic hematuria, and white blood cells in the urine. Macroscopic hematuria is rare, and for most patients, proteinuria is rated as “++” or higher. As the condition worsens, there is a decline in kidney function. In the later stages, the amount of protein in the urine gradually increases, with a daily loss of 3-4 grams or more, leading to swelling. Patients often experience high blood pressure, which further exacerbates kidney damage, ultimately leading to the occurrence of renal failure. In some cases, heart failure may also occur as a complication.

In the early stages of diabetic kidney disease, it is less likely to notice any signs or symptoms. Late-stage signs and symptoms may include:

  • Worsening blood pressure control
  • Urine with protein
  • Swelling in the feet, ankles, hands, or eyes
  • Increased frequency of urination
  • Reduced need for insulin or diabetes medications
  • Confusion or difficulty concentrating
  • Shortness of breath
  • Loss of appetite
  • Nausea and vomiting
  • Persistent itching
  • Fatigue

Additionally, in the late stages of diabetic kidney disease, there are often associated extrarenal symptoms such as cardiovascular complications, retinopathy, and peripheral neuropathy.

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Factors Accelerating the Progression of Diabetic Kidney Disease?

Unmodifiable Factors


The prevalence of diabetes increases with age. As China gradually enters an aging society, statistics show that in 2019, there were approximately 176 million people aged ≥65 in China, accounting for 12.6% of the total population. Among them, around 35.5 million had diabetes, constituting 25% of the global elderly diabetic population and ranking first worldwide. The risk of developing diabetic kidney disease (DKD) also rises with age. Studies have found a significant increase in proteinuria and a notable decrease in estimated glomerular filtration rate (eGFR) with advancing age. For every 5-10 years of age increase, the risk of DKD increases by 38%.

In a study involving 1398 type 2 diabetes patients, stratified by age, it was found that patients under 60 years old accounted for 46.2%, while those aged 60 and above accounted for 52.8%. The decline in eGFR was more significant than the occurrence of proteinuria, possibly due to the physiological decline in kidney function with age. Additionally, older individuals are more prone to concurrent chronic conditions such as hypertension, coronary heart disease, and cerebrovascular disease, which further exacerbate kidney damage.

Disease Progression

Increasing evidence suggests that the longer the duration of diabetes, the higher the risk of developing Diabetic Kidney Disease (DKD). Research indicates a significant correlation between a diabetes duration of >5 years and DKD, whereas a duration <5 years is usually associated with non-DKD conditions such as IgA nephropathy and membranous nephropathy. A prospective study in the UK found that from the time of diabetes diagnosis, the risk of progression to DKD at 5 years, 10 years, 15 years, 20 years, and 25 years was 17.3%, 24.9%, 28.0%, 34.3%, and 38.3%, respectively, showing a significant increasing trend. Other studies have indicated that individuals with type 1 diabetes rarely exhibit significant proteinuria within the first 10 years of the disease course. However, after 10 years, proteinuria gradually increases, and with intensified treatment, more than half of the population can recover to minimal or normal albuminuria over a follow-up period of up to 22 years. Therefore, although the duration of diabetes cannot be changed, proactive blood sugar management can lead to a reduction in proteinuria, helping alleviate kidney damage.


Most studies confirm a closer association between males and Diabetic Kidney Disease (DKD). Research indicates that the incidence of DKD is higher in males compared to females. In males, the average estimated glomerular filtration rate (eGFR) is lower, and the occurrence of proteinuria is higher. However, in females aged ≥60, the rate of eGFR < 30 ml∙min−1∙(1.73 m2)−1 is higher than in males of the same age. This may be related to sex hormones; estrogen, for instance, can protect the kidneys by improving creatinine clearance, reducing glomerulosclerosis and interstitial fibrosis, and decreasing proteinuria. On the other hand, androgens can induce podocyte damage, promote inflammation and interstitial fibrosis, accelerating the development of DKD.

Postmenopausal elderly women experience a decrease in estrogen, diminishing its protective effect. Animal studies have shown that supplementing estrogen in diabetic mice can inhibit glomerulosclerosis and reduce proteinuria, further confirming the protective role of estrogen in DKD. Additionally, there are gender differences in the distribution of adipose tissue, with females typically accumulating fat in the hips and thighs (pear-shaped), while males tend to accumulate it in the abdomen and viscera (apple-shaped). Some studies suggest that increased visceral fat in diabetic patients is associated with increased proteinuria. However, there are also studies finding no significant gender differences in the occurrence of DKD, and some even indicate a higher risk for females. Differences in research conclusions may be attributed to factors such as sample size and age stratification. Therefore, further research is necessary to deepen our understanding of the relationship between gender and DKD.

Genetic Factors

A family history of diabetes is an independent risk factor for the occurrence of Diabetic Kidney Disease (DKD). Increasing evidence suggests that genetic polymorphism plays a crucial role in the development of DKD. In the Han Chinese population with maturity-onset diabetes mellitus of the young (MODY), patients with COL4A3 gene variants exhibit poorer kidney function and higher levels of proteinuria. Animal experiments have identified DACH1 as a risk gene for kidney disease. In diabetic mouse models of kidney damage, the specific knockout of DACH1 in the kidneys exacerbates renal fibrosis, leading to a higher susceptibility to kidney disease.

In the epigenetic background studies of diabetes and its microvascular complications, microRNAs (miRNAs) are small endogenous non-coding single-stranded RNAs, and long non-coding RNAs (lncRNAs) are long non-coding RNAs that regulate gene expression. miR-34a plays a crucial role in the occurrence and development of DKD; downregulation of miR-34a can inhibit mesangial cell proliferation and alleviate glomerular hypertrophy. Significant changes in lncRNA expression occur in DKD mice, with 160 upregulated and 99 downregulated lncRNAs compared to diabetic mice. lncRNA8, lncRNA15, and lncRNA16 may be involved in the progression of DKD.

Compared to genetic factors, epigenetics is reversible and can provide diagnostic markers for DKD while offering new targets for treatment.

Modifiable Factors

Blood Glucose

Elevated blood glucose is a major modifiable factor contributing to the progression of Diabetic Kidney Disease (DKD). Poor blood glucose control can cause endothelial dysfunction and increased oxidative stress, leading to pathological and physiological changes in kidney structure, including thickening of the glomerular and tubular basement membranes, glomerulosclerosis, and tubular atrophy. Glycated hemoglobin (HbA1c) is a crucial indicator assessing the average blood glucose levels over the past 8-12 weeks.

In newly diagnosed type 2 diabetes patients, the UK Prospective Diabetes Study suggests that for every 1% decrease in average HbA1c, the risk of developing DKD decreases by 21%. Therefore, it is essential for diabetes patients to strive for optimal blood glucose control. Studies indicate that intensified blood glucose therapy can reduce the risk of DKD, but strict blood glucose control may have more drawbacks than benefits, such as an increased risk of hypoglycemia and mortality.

The specific HbA1c level that maximizes patient benefits remains controversial. Some research suggests that maintaining HbA1c levels below 7.0% is clinically significant in delaying the progression of DKD. However, for patients with poorer kidney function, mortality significantly increases when HbA1c levels are below 6.5% or above 8.0%. Therefore, blood glucose prevention and management for DKD should be stratified. Glycemic control strategies should consider factors such as the severity of the patient’s disease, the presence of complications, life expectancy, and the risk of hypoglycemia. Patients with better kidney function, fewer complications, longer life expectancy, and a lower risk of hypoglycemia may benefit from strict HbA1c control (<6.5%). On the other hand, patients with poorer kidney function, lower compliance, more complications, shorter life expectancy, and a higher risk of hypoglycemia may benefit more from a moderately relaxed blood glucose control target (HbA1c <8%).

Can Diabetes Cause Kidney Disease

Blood Pressure

Hypertension is another significant risk factor for Diabetic Kidney Disease (DKD). Regarding related mechanisms, the activation of the renin-angiotensin-aldosterone system, endothelial dysfunction, inflammation, and oxidative stress are all associated with kidney function damage. Studies examining different blood pressure variables have found that it is not diastolic pressure and mean arterial pressure but rather systolic pressure and pulse pressure that are relevant to the progression of DKD.

Further analysis of the variability in blood pressure, i.e., the extent of blood pressure fluctuations within a certain period, reveals that larger blood pressure fluctuations are associated with a higher risk of DKD development. The research suggests that for every 10-20 mmHg increase in systolic pressure, the risk of DKD increases by 21%. Lowering systolic pressure contributes to delaying the progression of DKD. However, intensified reduction of systolic pressure can significantly decrease estimated glomerular filtration rate (eGFR), increasing the risk of DKD in type 2 diabetes patients.

The optimal target for blood pressure control is a matter of debate. Some studies suggest that maintaining blood pressure at 140/85 mmHg provides the greatest kidney protection. Other research proposes a systolic pressure threshold of 127 mmHg, beyond which the risk of proteinuria significantly increases. The different target values may be attributed to variations in age, disease duration, underlying conditions, and other factors among the study populations.

In conclusion, clinicians and patients should focus on systolic pressure and pulse pressure when controlling blood pressure for DKD prevention. It is essential to enhance blood pressure monitoring, avoid excessive fluctuations, and maintain an appropriate blood pressure level based on the individual patient’s condition to achieve maximum protective effects.

Blood Lipids

The combination of diabetes and lipid metabolism disorders increases the risk of Diabetic Kidney Disease (DKD). Abnormal blood lipids typically refer to elevated triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), or decreased high-density lipoprotein cholesterol (HDL-C). The mechanism by which lipid metabolism disorders lead to kidney disease may involve an imbalance in lipid synthesis and uptake, resulting in lipid accumulation in renal tissue. Lipid deposition can increase oxidative stress, release inflammatory factors, and cause mesangial cell and endothelial cell damage, leading to glomerulosclerosis and tubular injury. Lipids can also affect podocyte function, impair the integrity of the glomerular filtration barrier, and contribute to proteinuria.

Studies have found that for every 1 mmol/L increase in TG, the risk of developing DKD increases by 42%, while for every 1 mmol/L increase in HDL-C, the risk decreases by 22%. Oxidized low-density lipoprotein (ox-LDL), a modification of LDL-C, can promote damage to glomeruli, tubules, and podocytes, resulting in proteinuria and loss of kidney function, making it an independent risk factor for DKD or end-stage kidney disease (ESKD). A recent study suggests that traditional lipid indicators may not fully reflect the risk of DKD. In comparison to traditional lipid indicators, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipid ratios appear to be more crucial.

Among various lipid indicators in type 2 diabetes patients, the LDL-C/ApoB ratio is closely related to DKD. This ratio is significantly correlated with estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR). A lower ratio indicates a higher risk of developing DKD. Therefore, it is essential to not only focus on traditional lipid indicators but also conduct further research on the correlation between apolipoproteins and lipid ratios with DKD.

kidney disease

Uric Acid

Uric acid (UA) is the final product of purine metabolism. When there is an excessive synthesis of UA or reduced excretion, it can lead to hyperuricemia. Hyperuricemia not only causes gout but also contributes to renal function impairment, accelerating the progression of Diabetic Kidney Disease (DKD). The mechanism involves the reduction of nitric oxide due to hyperuricemia, exacerbating inflammatory reactions, and causing endothelial dysfunction through increased oxidative stress.

A study that followed 422 diabetes patients with an average duration of 15 years for 43 months found that patients with initial hyperuricemia (SUA ≥ 420 μmol/l for males, ≥ 360 μmol/l for females) had a higher incidence of DKD and a faster progression to DKD. Another study indicated that elevated UA levels increase the risk of proteinuria, with a critical threshold of 6.9 mg/dL (410.55 μmol/l) for the development of DKD. Research on the relationship between hyperuricemia and DKD in adolescents with type 2 diabetes revealed that higher UA levels are an independent risk factor for increased urinary albumin excretion.

A prospective study in Japan investigating the relationship between serum UA levels and the occurrence and development of proteinuria in type 2 diabetes patients found that both higher and lower UA levels are associated with the progression of proteinuria. However, UA levels were not correlated with changes in estimated glomerular filtration rate (eGFR). In summary, hyperuricemia is a risk factor for the progression and deterioration of DKD. Lowering UA levels may have potential benefits for the progression of DKD, but the conclusion needs further confirmation through large-scale trials as excessively low UA levels may not provide additional protective effects and could potentially have adverse effects.


Obesity is an independent risk factor for DKD, with an estimated 603.7 million adults globally suffering from obesity according to epidemiological estimates. The World Health Organization typically defines obesity based on Body Mass Index (BMI). For every increase of 5 kg/m2 in BMI, the risk of developing DKD increases by 16%. However, BMI has limited differentiation in fat distribution and may not be the optimal indicator for measuring obesity. Studies have found that waist-to-hip ratio and waist-to-height ratio, representing central obesity, are more correlated with DKD compared to BMI. Additionally, there is a growing focus on visceral fat and subcutaneous fat, where an increase in visceral fat can lead to the accumulation of fat in organs such as the liver, heart, and pancreas, known as “ectopic fat deposition,” which can induce insulin resistance. Subcutaneous fat, on the other hand, helps prevent “ectopic fat deposition.”

Research indicates that in patients with type 2 diabetes, an increase in visceral fat is positively correlated with UACR (urinary albumin-to-creatinine ratio) and can serve as an indicator for screening DKD. Another study suggests that a higher ratio of visceral fat to subcutaneous fat is associated with a greater risk of developing DKD. Therefore, in clinical practice, it is crucial not only to assess the degree of obesity in patients but also to evaluate the type of obesity, with a focus on reducing visceral fat. Lifestyle changes, including a balanced diet and at least 150 minutes of moderate-intensity physical activity per week, are recommended for obese patients to control weight, improve insulin resistance, regulate blood sugar, and reduce complications.


Smoking is a risk factor for the occurrence of DKD. According to epidemiological statistics, approximately 7 million people die from smoking-related causes globally each year, and it is projected that by 2030, the death toll will reach 8.3 million. This is primarily due to tobacco smoke increasing inflammation and inducing oxidative stress, damaging endothelial function, ultimately leading to glomerulosclerosis and promoting the development of DKD. Smoking can also increase the expression of fibrotic cytokine TGF-β and extracellular matrix protein fibronectin, contributing to the progression of DKD.

Research has shown that diabetic patients who smoke have a 49% increased risk of developing DKD. The risk of DKD is dose-dependent on smoking, with light, moderate, and heavy smokers having incremental harms compared to diabetic patients who never smoked. Not only active smokers but an increasing number of people are exposed to secondhand smoke. Approximately 33% of non-smoking men, 35% of women, and 40% of children globally were exposed to secondhand smoke in 2004. The risk of eGFR decline is significantly higher in individuals exposed to secondhand smoke compared to those who are not exposed. Animal studies have demonstrated that diabetic mice exposed to tobacco smoke can accelerate the progression of DKD. It is advisable for diabetic patients who smoke to quit smoking as early as possible.

Studies have found that current smokers among diabetic patients consistently have poorer blood sugar control than those who quit smoking (abstinent for more than 3 months) and those who never smoked. Compared to diabetic patients who never smoked, current smokers have a 36% increased risk of DKD, while there is no significant difference in the risk of DKD between those who quit smoking and those who never smoked. This suggests that quitting smoking can improve the progression of existing kidney disease, but more in-depth research is needed to determine how long quitting smoking significantly reduces the risk of DKD. Regardless, the long-term benefits of quitting smoking are undeniable.

Therefore, it is essential to enhance health education for smokers, raise awareness of their health, encourage smoking cessation, and advocate for smoking bans in public places to better prevent the occurrence of DKD.

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Anemia is a common complication of DKD and is also a risk factor for the progression of DKD. Studies indicate that anemia can lead to renal tissue hypoxia through the induction of hypoxia-inducible factor-1 (HIF-1), exacerbating renal fibrosis and playing a significant predictive role in DKD. Serum erythropoietin (EPO) deficiency is a crucial factor in the occurrence of anemia-induced renal damage. Research has found that, compared to the high EPO group, patients in the low EPO group experience a significantly faster decline in eGFR. Injecting EPO into diabetic rats has been shown to inhibit inflammation and oxidative stress, improve renal interstitial fibrosis, and slow down the progression of DKD. Therefore, anemia can serve as an important therapeutic target to delay the onset of DKD.

Vitamin D

Vitamin D belongs to the group of steroid fat-soluble vitamins, primarily produced through exposure to ultraviolet light. Vitamin D deficiency not only leads to diseases like rickets and osteomalacia but also accelerates the progression of DKD. A study evaluating the correlation between serum 25-hydroxyvitamin D levels and DKD in type 2 diabetes patients found that the prevalence of DKD increased by approximately 21% in the group with vitamin D concentration < 50 nmol/L compared to those with vitamin D ≥ 50 nmol/L. For patients with insufficient vitamin D intake, supplementation may be appropriate because vitamin D can protect against DKD by inhibiting the activation of the renin-angiotensin system, thereby delaying glomerulosclerosis. A meta-analysis of 20 randomized controlled trials suggests that supplementing vitamin D or its analogs can reduce urinary protein excretion, but there is no apparent correlation with increasing eGFR. However, there is currently no conclusive clinical threshold for vitamin D deficiency or sufficiency related to DKD, and further research is needed to establish this.

Several risk factors can contribute to the occurrence and progression of DKD through different mechanisms, such as blood glucose, blood pressure, blood lipids, and uric acid, which can increase oxidative stress, activate the renin-angiotensin-aldosterone system, and damage the glomerular filtration barrier. Increased visceral fat leads to ectopic fat deposition, exacerbating insulin resistance, while smoking increases the expression of fibrotic cytokines. Anemia causes tissue hypoxia, aggravating renal fibrosis, among other effects. Most of these risk factors can be improved through proactive treatment and lifestyle changes. Therefore, early identification of risk factors for DKD and comprehensive management play a decisive role in reducing its incidence and mortality. This review summarizes the definition, staging, risk factors, and management of modifiable risk factors for DKD, providing guidance for clinical practice.

Effective Medicine diabetic kidney disease

Nonetheless, there is indeed a medication known as finerenone that has emerged to address this issue. Finerenone has broken this deadlock and offers hope for the treatment of diabetic kidney disease. Its first approved indication is for chronic kidney disease in type 2 diabetes patients. So, while traditional mineralocorticoid receptor antagonists like spironolactone may pose challenges in managing diabetic kidney disease due to the risk of hyperkalemia, finerenone has shown promise in this regard and has gained approval for this specific use.

LUCIFINE finerenone tablets
LUCIFINE finerenone tablets

Finerenone improves chronic kidney disease associated with type 2 diabetes
Finerenone, developed by the German pharmaceutical company Bayer, is a new-generation, non-steroidal, selective mineralocorticoid receptor antagonist. It is also known as finerenone or finerenone. It was approved for market launch in July of the previous year.

To answer how finerenone improves chronic kidney disease related to type 2 diabetes, we first need to understand the mechanism of mineralocorticoids and their action. Mineralocorticoids are substances secreted by the zona glomerulosa of the adrenal cortex, with aldosterone being the primary representative.

Aldosterone’s target organs include the kidneys, heart, salivary glands, gastrointestinal secretory glands, and others, and it is regulated by the renin-angiotensin-aldosterone system, blood potassium ions, and blood sodium ions. When aldosterone secretion increases, its effects on the kidneys lead to increased reabsorption of sodium and water, increased excretion of potassium ions, resulting in fluid and sodium retention, hypernatremia (high sodium levels in the blood), hypokalemia (low potassium levels in the blood), and metabolic alkalosis, among other effects. This can contribute to kidney damage.

Finerenone works by selectively blocking the mineralocorticoid receptor, reducing the harmful effects of aldosterone on the kidneys and other target organs. By doing so, it helps mitigate the progression of kidney disease in type 2 diabetes patients, providing a novel approach to treating this condition.

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How to Find Affordable and Highly Effective finerenone

It’s widely known that the treatment for type 2 diabetes, RYBELSUS® (semaglutide) tablets, comes with a high cost of up to $995 for 30 tablets. Similarly, the medication for treating diabetic kidney disease, Kerendia finerenone tablets, can be as expensive as $670 for 30 tablets. The exorbitant prices of these medications undoubtedly add to the challenges faced by patients in their daily lives.

Is there an equally effective but more affordable medication available? The answer is LUCIFINE finerenone tablets produced by Lucius Pharmaceuticals. LUCIFINE finerenone tablets are a diabetes kidney disease treatment that has received approval from the Laotian Ministry of Health and is manufactured in Lucius Pharmaceuticals’ GMP factory in Laos, as approved by the U.S. FDA.

LUCIFINE finerenone tablets are not only a legitimately authorized medication but also come at a very affordable price, being only one-third the cost of Kerendia finerenone tablets while delivering the same efficacy.

DKD Care Center serves as the authoritative global distributor for LUCIFINE finerenone tablets, and we possess the necessary authorization certificates from Lucius Pharmaceuticals. The introduction of this new medication comes with significant discounts. If you have been suffering from diabetic kidney disease for an extended period, please don’t hesitate to contact us promptly:

Phone: +852 6993858

Whatsapp: +852 9506 4225



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