Summary And Inventory Of Chronic Kidney Disease Treatment Progress And Guidelines in 2023

Chronic kidney disease (CKD) affects about 10% of the world's population, placing a huge burden on global society and individuals. Doctors and scholars around the world are very concerned about this and spend a lot of time, energy, and money studying the treatment of CKD every year, and this year is no exception.

Click to Cistanche for kidney disease

At the end of 2023, BMJ released a comprehensive summary of CKD treatment progress in 2023, summarizing the definition and causes of CKD, treatment goals, treatment guidelines, and research progress on therapeutic drugs.

Definition and causes of CKD

Before clarifying the treatment progress of CKD, the definition and components of CKD should first be clarified. Currently, CKD is defined as abnormalities in kidney structure or function that persist for more than 3 months, manifested by low glomerular filtration rate (GFR) or the presence of markers of kidney damage. The specific diagnostic criteria for CKD must meet at least one of the following:

CKD diagnostic criteria

Urinary albumin to creatinine ratio (UACR) ≥30mg/g;

Albumin excretion in 24 hours ≥30mg;

GFR＜60ml/min/1.73㎡;

Urinary sediment, renal histology, or imaging abnormalities;

Electrolyte or other abnormalities caused by renal tubular disorders;

History of kidney transplantation.

Generally speaking, the etiology of CKD is complex. Doctors should determine the cause through imaging, extrarenal manifestations, biomarkers, renal biopsy, and other means. Etiological classification generally depends on whether the patient presents with systemic disease, such as obesity, diabetes, hypertension, or autoimmune disease, and the specific location of the renal pathology, such as glomeruli, tubules, renal vessels, or cystic/congenital anomalies. Unfortunately, for most patients with CKD, the cause is not identified. This limits the treatment of CKD. It is worth noting that in recent years, phenotyping and genetic testing have been increasingly used to assist in the diagnosis of the cause of CKD. One study suggests that 34% of CKD patients will have their cause reconfirmed based on genetic testing results. At the end of 2022, the European Renal Association (ERA) and the European Rare Kidney Disease Reference Network (ERKDRN) jointly issued a consensus recommending that the following CKD patients should receive genetic testing:

Circumstances requiring genetic testing

renal tubular disease;

Glomerular diseases, including congenital nephrotic syndrome, glucocorticoid-refractory nephrotic syndrome, and multi-organ-resistant glucocorticoid-refractory nephrotic syndrome;

Complement disorders, including immune complex-mediated membranoproliferative glomerulonephritis, C3 glomerulonephritis, and atypical hemolytic uremic syndrome (aHUS);

Renal ciliopathies;

congenital renal and urinary tract malformations;

Patients under 50 years old with severe CKD of unknown cause;

Patients >50 years old, with new-onset CKD, and with a family history of kidney disease.

treatment goals

There are two treatment goals for CKD: cause treatment and symptomatic treatment. Treatment of the cause is individualized. For patients whose cause has been identified, treatment of the cause can greatly improve the progression of CKD and even calculate the approximate time of progression to end-stage renal disease (ESRD), which is beneficial to patient management. Symptomatic treatment is management that all CKD patients need to receive, such as blood pressure control, blood sugar control (if combined with diabetes), etc

01 Treat the cause

Determining the cause of CKD is critical because different causes of CKD have different prognoses and different treatments. For example, autosomal dominant polycystic kidney disease (ADPKD), the most common genetic cause of CKD, often progresses more quickly than other diseases. The treatment of ADPKD is significantly different from other CKD. In terms of medication, tolvaptan needs to be added, and dietary intervention requires increasing the intake of a large amount of fluids. Immunoglobulin A (IgA) nephropathy is the most common glomerulonephritis in countries in East Asia and the Pacific. Some recent studies have suggested that APOL1-related gene variants (common in African Americans) may be the cause of some IgA nephropathy. A recently published phase 2A study of targeted therapy for APOL1-related disease showed a trend toward reduced albuminuria in IgA nephropathy patients with APOL1 gene variants. In addition, patients with lupus nephritis need to be treated with belimumab, while patients with primary hyperoxaluria need to be treated with lumasiran. There is a high probability that the above drugs will not appear in the prescriptions of other CKD patients.

In summary, clarifying the cause of the disease can enable precision medicine and help doctors manage CKD patients.

02 Symptomatic treatment

Symptomatic treatment is mainly to correct the risk factors that lead to the progression and complications of CKD, such as dietary control, increased exercise, weight management, blood pressure management, weight management, and lipid management.

Among the above intervention and treatment models, four key points require special attention:

①Blood pressure control

Current evidence shows that intensive blood pressure control fails to slow the rate of decline in GFR in all patients with CKD, but the Modification of Diet in Renal Disease Study (MDRD) found that in patients with baseline proteinuria ≥3 g/d, intensive blood pressure lowering Can slow down the rate of decline of GFR. This suggests that intensive blood pressure lowering may be more beneficial for CKD patients with massive proteinuria.

In addition, blood pressure control is an important means to intervene in the occurrence and progression of cardiovascular diseases in CKD patients. The SPRINT study revealed that although there was no significant difference in the risk of composite renal outcomes in patients with CKD between the systolic blood pressure (SBP) target group <140 mmHg and the SBP target group <120 mmHg, patients in the SBP <140 mmHg group experienced composite cardiovascular outcomes and all-cause outcomes. Lower risk of death!

②Blood sugar management

In patients with diabetes and CKD, blood sugar control is an important part of comprehensive treatment. The ADVANCE study revealed that for 11,140 patients with diabetes (19% eGFR <60ml/min/1.73㎡, 31% of patients had proteinuria at baseline), intensive glycemic control was associated with a reduced risk of end-stage renal disease compared with standard glycemic control. 65% correlation (HR=0.35; 95%CI 0.15-0.83).

③Avoid nephrotoxic drugs

Many drugs are eliminated by glomerular filtration or tubular secretion. Reduced glomerular filtration rate can lead to the accumulation of drugs or their metabolites, resulting in adverse reactions. Special attention should be paid when some antiviral, antibiotic drugs, oral anticoagulants, chemotherapy drugs, and diabetes drugs are given to CKD patients, and the dosage of the above drugs needs to be adjusted according to eGFR. The U.S. Food and Drug Administration (FDA) advises that it is not recommended to use creatinine clearance estimated by the Cockcroft-Gault equation to adjust the dosage of the above drugs.

People with CKD should avoid or minimize the use of certain medications to reduce the risk of worsening kidney function. Nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided when patients with CKD are treated with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) + diuretics. In addition, proton pump inhibitors (PPIs) may cause acute or chronic interstitial nephritis. Although the mechanism is unknown, most experts believe that PPIs should be used with caution in patients with CKD.

④Lipid management

The SHARP study revealed that statins can safely and effectively lower lipids in CKD patients (33% receiving dialysis) with a mean eGFR of 27ml/min/1.73㎡. Compared with placebo, the intervention group experienced the first major atherosclerosis. The risk of events was significantly reduced by 17%.

guideline treatment

The current CKD guidelines mainly come from the Kidney Disease Improving Global Outcomes Organization (KDIGO) the British National Institute for Health and Clinical Excellence (NICE), the American College of Cardiology, the American Heart Association, the European Society of Cardiology, the European Society of Hypertension, International High School Blood Pressure Society, American Diabetes Association (ADA).

Experts summarized the above guidelines and found that 7 opinions are widely recommended:

Widely recommended opinions

① Diabetic patients should receive CKD screening at least once a year, and special reminders should include proteinuria testing;

②Test anyone at risk for CKD, including those with hypertension, cardiovascular disease, diabetes, and a history of acute kidney injury.

For CKD patients, proteinuria testing must be done once a year;

④SBP should be <130mmHg, especially if UACR≥70mg/mmol, the blood pressure target is <130/80mmHg.

⑤NICE guidelines and KDIGO guidelines recommend ACEi/ARB as first-line antihypertensive therapy for patients without diabetes but with proteinuria and for patients with diabetes and CKD stages G1-G4.

⑥KDIGO and ADA guidelines recommend that the first-line treatment drug for all CKD patients with type 2 diabetes (eGFR ≥ 20ml/min/1.73㎡) is a sodium-glucose co-transporter 2 inhibitor (SGLT-2i). NICE guidelines recommend that if UACR is >30 mg/mmol, SGLT-2i should be used. If UACR is between 30 and 300 mg/g, SGLT-2i should be considered.

⑦KDIGO guidelines further point out that once SGLT-2i is started, even if the patient's eGFR is <20ml/min/1.73㎡, as long as it is tolerated and renal replacement therapy is not performed, the patient can continue to receive SGLT-2i treatment.

Research progress of therapeutic drugs

In recent years, research on CKD treatment drugs has progressed rapidly, but 5 drugs require special attention. This article mainly summarizes their clinical precautions:

①ACEi and ARB

ACEi can reduce the risk of renal replacement therapy by 30%, ARB can prevent the progression of CKD and can prevent cardiovascular disease in CKD patients. However, in clinical practice, patients should avoid using ACEi and ARB simultaneously to prevent hyperkalemia and acute kidney injury.

②SGLT-2i

Recent clinical studies have found that for baseline eGFR <20ml/min/1.73㎡, SGLT-2i can reduce the risk of adverse renal outcomes by approximately 30%. In addition, SGLT-2i can be used in combination with ACEi/ARB, which can be additive in delaying the progression of CKD. Existing data indicate that SGLT-2i has no significant safety risk, but it should be noted that SGLT-2i may lead to a slightly increased risk of genital infection in CKD patients.

③Glucagon-like peptide-1 receptor agonist

Glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to improve renal outcomes in patients with type 2 diabetes, reducing the risk of renal outcomes (including albuminuria) by 15% to 36%. However, the exact mechanism by which GLP-1RA delays eGFR decline and/or proteinuria reduction is unclear.

④Mineralocorticoid receptor antagonists

Mineralocorticoid receptor antagonists (MRA) can be used as auxiliary treatments for ACEi or ARB, especially for patients with albuminuria and/or diabetes. Two common steroidal nonselective MRAs, spironolactone, and eplerenone, both reduce albuminuria.

But even more eye-catching is the non-steroidal MRA, fenelinone. Existing evidence suggests that fenelidone reduces the risk of the composite renal outcome by 15-23%. Moreover, for CKD patients with type 2 diabetes, the combined use of fenelidone and SGLT-2i or GLP-1RA will not affect the efficacy of each other, and it is even possible that 1+1>2.

⑤Endothelin receptor antagonist

Endothelin receptor antagonists have emerged as novel treatments for a variety of kidney diseases. For example, the SONAR study evaluated the impact of Atrasentan (tentative translation: Atrasentan) in patients with type 2 diabetes and found that compared with the placebo group, the composite renal outcome (doubling of serum creatinine or ESKD) in the atrasentan group was The risk is reduced by 35%.

Another endothelin receptor antagonist, Sparsentan (tentative name: Sparsentan), has special effects on IgA nephropathy and focal segmental glomerulosclerosis (FSGS), and compared with irbesartan, it can reduce proteinuria is stronger.

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.

Furthermore, cistanche has been shown to have immunomodulatory effects. In kidney disease, the immune system can be dysregulated, leading to excessive inflammation and tissue damage. Cistanche helps regulate the immune response by modulating the production and activity of immune cells, such as T cells and macrophages. This immune regulation helps reduce inflammation and prevent further damage to the kidneys.

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.