How To Correctly Evaluate And Manage CKD Patients After Successful Weight Loss?

Currently, many patients with chronic kidney disease (CKD) are obese or overweight, and glucagon-like peptide 1 receptor agonists (GLP-1RA) and GLP/gastric inhibitory peptide (GIP) dual receptor agonists are effective in type 2 Their use in the treatment of diabetes and obesity has increased dramatically, and they can not only significantly reduce weight but also significantly improve renal outcomes in obese CKD patients. However, significant weight loss in the short term will affect the assessment of estimated glomerular filtration rate (eGFR) and urinary albumin excretion (UAE), thereby having certain implications for the management of CKD patients.

Click to Cistanche for kidney disease

On January 31, 2024, NDT published an editorial from the University of Michigan in the United States, which pointed out that there are 4 key points to pay attention to when evaluating CKD patients who have successfully lost weight!

4 things to note

① Renal function assessment should measure GFR (mGFR) or eGFR assessed by creatinine + cystatin C;

② Due to significant changes in body shape and body surface area, the eGFR of this type of patient should be removed from the body surface area and only assessed by GFR (ml/min);

③ Evaluation should be carried out in groups according to whether the patients are in an ultrafiltration state at baseline;

④ When evaluating patients' proteinuria and renal function, changes in blood pressure, blood sugar, and inflammatory markers should also be combined.

Assessment of GFR

Currently, there are two main methods to evaluate GFR. The first method is exogenous biomarkers, such as iohexol. The glomerulus freely filters Iohexol and is neither secreted nor reabsorbed, but measuring GFR using exogenous filtration markers is more expensive and less accessible. The second approach is endogenous biomarkers such as creatinine and cystatin C.

Of note, endogenous biomarkers are less reliable in assessing renal function in patients with large body weight or significant weight loss. Creatinine is a waste product produced by the breakdown of muscles and is filtered by the kidneys. Studies have found that in patients with gross body weight and weight loss, muscle mass is reduced and creatinine production is reduced, resulting in lower serum and urinary creatinine levels. This may result in a significant increase in creatinine eGFR in obese individuals who lose weight. Cystatin C is an endogenous protein produced at a constant rate by all nucleated cells and can be used as a surrogate or secondary biomarker for creatinine to estimate GFR. Unlike creatinine, cystatin C is not affected by muscle mass, dietary protein consumption, or exercise, but epidemiological studies have shown that it is associated with body mass index (BMI). Therefore, patients with reduced BMI may have a significant decrease in cystatin C and a significant increase in eGFR.

Chang et al found that creatinine and cystatin c assessment of GFR may be biased in previously obese patients who have successfully lost weight. In a study of patients undergoing bariatric surgery, researchers used iohexol to measure GFR (mGFR) and creatinine, cystatin c, and the CKD-EPI formula to calculate eGFR. Before surgery, the average BMI of the enrolled patients was 49.5kg/㎡, which dropped to 35.6kg/㎡ after surgery. After surgery, mGFR increased slightly, but eGFR of creatinine, cystatin c, and creatinine + cystatin C all increased significantly. It is worth noting that the eGFR of creatinine + cystatin C is closest to mGFR. It is suggested that eGFR and mGFR of creatinine + cystatin C are suitable for evaluating renal function in CKD patients with successful weight loss and previous obesity.

body surface area changes

Currently, the commonly used unit for eGFR expression is ml/min/1.73㎡, where 1.73㎡ is the body surface area (BSA). GFR is routinely normalized to BSA and then expressed so that numerical expression can be expressed in individual body weights of different body types. However, this assessment method seems inappropriate for modern obese people and people who have successfully lost weight. There are two reasons. First, the BSA of 1.73㎡ was the average BSA of the American population nearly 100 years ago, while the BSA of the modern population has undergone major changes. According to relevant data from the U.S. National Health and Nutrition Database from 2015 to 2018, the average BSA of American women is 1.78㎡ (IQR: 1.64~1.94), and the average BSA of men is 2.03㎡ (IQR: 1.88~2.20). Therefore, it seems inappropriate to use the standards of nearly 100 years ago to evaluate the eGFR of modern people, especially obese people.

Second, BSA changes with significant changes in BMI. For example, a man with a BMI of 40kg/㎡ and a BSA of 2.41. If his GFR is 90ml/min, his eGFR is 65ml/min/1.73㎡. When he successfully loses weight his height remains unchanged, and his BMI is 20kg/㎡, if his GFR is still 90ml/min, his eGFR is 87ml/min/1.73㎡. It can be seen that if the BSA is not removed, then simply losing weight can increase the patient's eGFR by 22 ml/min/1.73㎡, which will significantly affect the doctor's evaluation of his renal function.

So, how to remove the impact of BSA on GFR? Experts suggest that this can be achieved by multiplying the eGFR by the patient's actual BSA and dividing by 1.73. This avoids the significant impact of changes in patients' BSA before and after weight loss on their eGFR, allowing for a more accurate assessment of longitudinal changes in renal function in CKD patients.

Subgroup analysis of ultrafiltration

It is well known that both obesity and diabetes may lead to glomerular hyperfiltration. Ultrafiltration and eGFR generally decrease with weight loss, and because BSA also decreases with weight loss, there is usually no significant difference in eGFR in patients after weight loss. However, when eGFR is not indexed by the BSA of 1.73㎡, it is particularly important whether there is high filtration at the baseline. It is worth noting that if the patient's eGFR is >120ml/min/1.73㎡ or <60ml/min/1.73㎡ before successful weight loss, the reasons for the change in eGFR before and after weight loss may be completely different. If the two are confused, It may be difficult to correctly interpret the cause of changes in a patient's eGFR, leading to different management options. Therefore, the best solution is to separately analyze eGFR changes in patients with and without hyperfiltration at baseline.

Relationship between changes in proteinuria and other indicators

A large number of studies have shown that regardless of the weight loss method adopted, UAE and urinary albumin to creatinine ratio (UACR) will decrease after weight loss. Furthermore, reduced UACR occurs despite loss of muscle mass and lower urinary creatinine levels. A randomized controlled study compared the relationship between bariatric surgery and drug treatment (such as sodium-glucose co-transporter 2 inhibitors, GLP-1RA, etc.) and patients' albuminuria remission rate (UACR <30mg/g). The results found that bariatric surgery can also successfully reduce patients' UACR, and there is no significant difference from drug treatment. In addition, weight loss reduced proteinuria levels regardless of whether patients had diabetes at baseline. Therefore, the effects of weight loss on blood glucose and blood pressure can only explain part of the reduction in proteinuria. Studies have found that an important reason for the reduction in proteinuria caused by weight loss may be related to the reduction of inflammatory markers, such as high-sensitivity C-reactive protein. It is suggested that weight loss itself can reduce vascular inflammation and thereby reduce proteinuria.

In short, when evaluating proteinuria in patients who have successfully lost weight, blood glucose, blood pressure, and inflammatory markers should be combined to clarify the reasons for the reduction in proteinuria, so that correct management decisions can be made.

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.