Progress in Diagnosis And Treatment Of Diabetic Nephropathy

On March 30, Professor Wang Rong from Shandong Provincial Hospital gave a lecture on "Progress in Diagnosis and Treatment of Diabetic Nephropathy" at the 11th West Lake Forum on New Advances in Nephrology.

1. Progress in understanding from DN to DKD

Professor Wang Rong said that in recent years, due to the significant increase in the number of diabetic patients worldwide, diabetes has become the main cause of diabetic kidney disease (DKD), causing serious harm. However, due to the complex pathogenesis of DKD and the lack of specific intervention targets, the treatment effect is not ideal, and it faces great challenges in the clinical prevention and treatment process. The traditional concept is that diabetic nephropathy (DN) is a microvascular complication caused by diabetes, but with the deepening of clinical research, the 2007 National Kidney Foundation/KDOQI Guidelines believe that DKD refers to chronic kidney disease caused by diabetes; diabetes Glomerular disease refers to changes in the glomeruli caused by diabetes that are confirmed by kidney biopsy. In 2014, the American Diabetes Association and the National Kidney Foundation reached a consensus, stating that the diagnosis of DKD includes an estimated glomerular filtration rate (eGFR) <60 ml/(min·1.732) or a urinary albumin-to-creatinine ratio higher than 30 mg. /g lasts for more than 3 months.

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The diagnosis of DN is mainly based on pathological features and is defined by the presence of proteinuria with retinopathy in patients with type 1 diabetes. The presence of proteinuria is considered an early sign of typical diabetic glomerulopathy, which is characterized by glomerular basal Membrane thickening, endothelial injury, mesangial hyperplasia and nodules, and podocyte loss. The diagnosis of DKD is based on clinical characteristics and is diagnosed by albuminuria and/or eGFR on the basis of diabetes. According to the latest definition of the 2020 KDIGO clinical practice guideline, DKD does not specifically refer to pathological phenotypes, including non-classical glomerular lesions. and tubulointerstitial disease. It can be seen that DKD is a first-level understanding of DN update.

2. Understanding from irreversible to reversible urinary microprotein

The timeline is well characterized for type 1 diabetes; for type 2 diabetes, the timeline may deviate. It was previously believed that moderately elevated urinary albumin was the earliest clinically detectable biomarker of typical diabetic glomerulopathy. Later studies found that a rapid decline in eGFR has more prognostic value, because eGFR may decrease before or without albuminuria and even progress to end-stage renal disease.

Currently, the development of microalbuminuria is no longer considered an irreversible stage of DKD, and spontaneous remission of microalbuminuria is reported as a common occurrence. Studies have shown that the remission rate of microalbuminuria in patients with type 1 or type 2 diabetes ranges from 21% to 64%. However, the reversal of proteinuria in type 1 and type 2 diabetes is different. In type 1 diabetes, a moderate increase in urinary microalbumin to normal levels is a common phenomenon. This phenomenon also occurs in type 2 diabetes, but the incidence is lower than that of type 1. In a cohort of 386 patients with type 1 diabetes who had moderately elevated urinary albumin, 59% resolved to mild levels of albuminuria after 6 years, and only 19% progressed to severely elevated urinary albumin.

Factors affecting urinary protein excretion include hypoglycemia: glycated hemoglobin <8%; hypotension: systolic blood pressure <115 mmHg (1 mmHg=0.133 kPa); hypolipidemia: total cholesterol <5.12 mmol/L, triacylglycerol <1.64 mmol/ L, Urinary protein excretion rates can be consistently reduced in patients receiving medications such as renin-angiotensin system blockers. In addition, the remission of proteinuria is also related to the reduction of eGFR decline, and controlling blood pressure and improving blood sugar are independent predictors of proteinuria remission.

3. Non-albuminuric DKD and albuminuric DKD

Judging from the current clinical data, albuminuric DKD and albuminuric DKD show the following characteristics: (1) Compared with albuminuric DKD, the prevalence of diabetic retinopathy in non-albuminuric patients is lower (10 respectively) %～43% and 22%～62%), the prevalence of large blood vessels is similar. (2) A study conducted renal biopsy on diabetic patients with normal albumin excretion and found that pathological manifestations include typical diabetic glomerular lesions, lesions mainly involving blood vessels and renal tubulointerstitium, and non-specific lesions. (3) DKD appears to progress more slowly in diabetic patients without albuminuria. In addition, patients with both non-albuminuric DKD and albuminuric DKD are at increased risk of cardiovascular events.

4. Clinical diagnosis and progress of DKD

1. Rule out diagnosis

Diabetes combined with kidney damage cannot be defined as DKD. If any of the following conditions occur, other causes should be considered. (1) Severe albuminuria (i.e. >300 mg/d or mg/g) within 5 years of the onset of type 1 diabetes. (2) eGFR decreases rapidly [eGFR decreases >5 ml/(min·1.73m2) per year]. (3) Proteinuria increases sharply or nephrotic syndrome occurs. (4) The urine sediment shows signs of activity such as abnormal red blood cells and white blood cell casts. (5) Symptoms or signs of other systemic diseases, such as systemic lupus erythematosus.

2. Diagnostic criteria

Persistent urinary microalbumin and/or persistent decrease in eGFR includes: (1) If regular urine sample collection and measurement are used, albuminuria is defined as urinary albumin ≥ 30 mg/d. (2) If the random urine albumin/creatinine ratio is used to estimate the excretion rate, it is defined as a ratio >30 mg/g. (3) Reduced eGFR is defined as eGFR <60 ml/(min·1.73m2) measured using a creatinine-based formula. (4) Albuminuria or reduced eGFR persists for at least 3 months.

3. Progress in clinical diagnosis of DKD

Albuminuria and low eGFR have poor sensitivity in diagnosing early DKD, hindering the diagnosis and prediction of early DKD and affecting the development of new research on early treatment and prevention of the disease. Several circulating and urinary biomarkers are currently in clinical development as diagnostic and prognostic tools, but none are currently in clinical use. Progress in the clinical diagnosis of DKD includes the following aspects: (1) In addition to urinary albumin, glomerular injury markers also include urinary transferrin, urinary IgG, and urinary type IV collagen. (2) Inflammation and fibrosis markers are independent predictors of CKD progression in type 1 diabetes and type 2 diabetes. (3) High-risk CKD273 score is closely related to the occurrence of albuminuria in type 2 diabetes. (4) Serum galectin-3 levels, which are involved in promoting renal and cardiac fibrosis, are independently associated with doubling of blood creatinine and proteinuria events in type 2 diabetes. (5) Inflammatory mediators are involved in the occurrence and development of DKD to varying degrees, such as TNF-a, IL-1, IL-6, and IL-18. (6) Fibrosis mediators such as TGF-β1 are the key to fibrosis in diabetic kidney injury.

5. Clinical Treatment of DKD

Regarding the treatment of DKD, Professor Wang Rong introduced the following points:

(1) Hypoglycemic management of DKD. Non-dialysis patients: Emphasis on individualized control. Non-dialysis patients should control glycated hemoglobin (HbA1c). For those who are at risk of hypoglycemia, it is not recommended that HbA1c be lower than 7.0%, as their life expectancy is shorter. For those with comorbidities and risks of hypoglycemia, the HbA1c control target should be appropriately relaxed, no more than 7% to 9 %. Dialysis patients: The optimal HbA1c related to the prognosis of dialysis patients has not yet been determined. It is recommended to set the HbA1c target at 7% to 8%; for patients who are relatively young (<50 years old) and have no obvious comorbidities, an HbA1c close to 7% is recommended. Goal: In older patients with multiple comorbidities, HbA1c targets approach 8%.

(2) Drug treatment. Renin-angiotensin system blockers have been the cornerstone of DKD management for decades, based on high-quality randomized studies. For patients with type 1 or type 2 diabetes accompanied by DKD and severely elevated urinary albumin, it is recommended that the antihypertensive regimen include angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB). Avoid coadministration of ACE inhibitors and ARBs, nor should one of these drugs be combined with a renin-angiotensin system blocker. For patients with type 2 diabetes who still have DKD and severely elevated urinary albumin despite angiotensin suppression, sodium-glucose cotransporter 2 is recommended. In DKD patients with reduced eGFR, glucagon-like peptide-1 receptor agonists can significantly improve cardiovascular and renal outcomes while controlling blood glucose. In the future, there will be some progress in clinical drug treatment research, including non-selective phosphodiesterase inhibitors, vitamin D analogs, advanced glycation end-product inhibitors, endothelin receptor inhibitors, etc., and the future is expected to be clinically application on.

6. Summary

Finally, Professor Wang Rong concluded as follows: (1) The clinical outcomes of DKD vary greatly, and the natural course of the disease is not single or unidirectional. (2) Factors that contribute to the resolution of albuminuria in DKD: better blood sugar control, lower blood pressure, lower total cholesterol and triacylglycerol levels. (3) Less emphasis should be placed on the mechanism of proteinuria, and more attention should be paid to the mechanism that initiates and promotes early decline in renal function and ultimately develops into end-stage renal disease. (4) For patients with type 1 or type 2 diabetes accompanied by DKD and severely elevated urinary albumin, it is recommended that the antihypertensive regimen include ACEI or ARB. Combination use of ACEI or ARB should be avoided, and one of these drugs should not be used with renin-angiotensin. combined with hormone system blockers. (5) For patients with type 2 diabetes who still have DKD and severely elevated urinary albumin after using angiotensin inhibitors, sodium-glucose cotransporter 2 is recommended. (6) In DKD patients with reduced eGFR, glucagon-like peptide-1 receptor agonists can significantly improve cardiovascular and renal outcomes while controlling blood sugar.

How Does Cistanche Treat Kidney Disease?

Cistanche is a traditional Chinese herbal medicine used for centuries to treat various health conditions, including kidney disease. It is derived from the dried stems of Cistanche deserticola, a plant native to the deserts of China and Mongolia. The main active components of cistanche are phenylethanoid glycosides, echinacoside, and acteoside, which have been found to have beneficial effects on kidney health.

Kidney disease, also known as renal disease, refers to a condition in which the kidneys are not functioning properly. This can result in a buildup of waste products and toxins in the body, leading to various symptoms and complications. Cistanche may help treat kidney disease ase through several mechanisms.

Firstly, cistanche has been found to have diuretic properties, meaning it can increase urine production and help eliminate waste products from the body. This can help relieve the burden on the kidneys and prevent the buildup of toxins. By promoting diuresis, cistanche may also help Reduce high blood pressure, a common complication of kidney disease.

Moreover, cistanche has been shown to have antioxidant effects. Oxidative stress, caused by an imbalance between the production of free radicals and the body's antioxidant defenses, plays a key role in the progression of kidney disease. ies help neutralize free radicals and reduce Oxidative stress, thereby protecting the kidneys from damage. The phenylethanoid glycosides found in cistanche have been particularly effective in scavenging free radicals and inhibiting lipid peroxidation.

Additionally, cistanche has been found to have anti-inflammatory effects. Inflammation is another key factor in the development and progression of kidney disease. Cistanche's anti-inflammatory properties help reduce the production of pro-inflammatory cytokines and inhibit the activation of inflammation mandatory pathways, thus alleviating inflammation in the kidneys.

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Moreover, cistanche has been found to improve renal function by promoting the regeneration of renal tubes with cells. Renal tubular epithelial cells play a crucial role in the filtration and reabsorption of waste products and electrolytes. In kidney disease, these cells can be damaged, leading to damaged renal function. Cistanche's ability to promote the regeneration of these cells helps restore proper renal function and improve overall kidney health.

In addition to these direct effects on the kidneys, cistanche has been found to have beneficial effects on other organs and systems in the body. This holistic approach to health is particularly important in kidney disease, as the condition often affects multiple organs and systems. che has been shown to have protective effects on the liver, heart, and blood vessels, which are commonly affected by kidney disease. By promoting the health of these organs, cistanche helps improve overall kidney function and prevent further complications.

In conclusion, cistanche is a traditional Chinese herbal medicine used for centuries to treat kidney disease. Its active components have diuretic, antioxidant, anti-inflammatory, immunomodulatory, and regenerative effects, which help improve renal function and protect the kidneys from further damage. , cistanche has beneficial effects on other organs and systems, making it a holistic approach to treating kidney disease.